Long non-coding RNAs(lncRNAs),which represent a new frontier in molecular biology,play important roles in regulating gene expression at epigenetic,transcriptional and post-transcriptional levels.More and more lncRNAs ...Long non-coding RNAs(lncRNAs),which represent a new frontier in molecular biology,play important roles in regulating gene expression at epigenetic,transcriptional and post-transcriptional levels.More and more lncRNAs have been found to play important roles in normal cell physiological activities,and participate in the development of varieties of tumors and other diseases.Previously,we have only been able to determine the function of lncRNAs through multiple mechanisms,including genetic imprinting,chromatin remodeling,splicing regulation,mRNA decay,and translational regulation.Application of technological advances to research into the function of lncRNAs is extremely important.The major tools for exploring lncRNAs include microarrays,RNA sequencing(RNA-seq),Northern blotting,real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR),fluorescence in situ hybridization(FISH),RNA interference(RNAi),RNA-binding protein immunoprecipitation(RIP),chromatin isolation by RNA purification(ChIRP),crosslinking-immunopurification(CLIP),and bioinformatic prediction.In this review,we highlight the functions of lncRNAs,and advanced methods to research lncRNA-protein interactions.展开更多
AIM: To screen and investigate the effective g RNAs against hepatitis B virus(HBV) of genotypes A-D.METHODS: A total of 15 g RNAs against HBV of genotypes A-D were designed. Eleven combinations of two above g RNAs(dua...AIM: To screen and investigate the effective g RNAs against hepatitis B virus(HBV) of genotypes A-D.METHODS: A total of 15 g RNAs against HBV of genotypes A-D were designed. Eleven combinations of two above g RNAs(dual-g RNAs) covering the regulatory region of HBV were chosen. The efficiency of each g RNA and 11 dual-g RNAs on the suppression of HBV(genotypes A-D) replication was examined by the measurement of HBV surface antigen(HBs Ag) or e antigen(HBe Ag) in the culture supernatant. The destruction of HBV-expressing vector was examined in Hu H7 cells co-transfected with dual-g RNAs and HBVexpressing vector using polymerase chain reaction(PCR) and sequencing method, and the destruction of ccc DNAwas examined in Hep AD38 cells using KCl precipitation, plasmid-safe ATP-dependent DNase(PSAD) digestion, rolling circle amplification and quantitative PCR combined method. The cytotoxicity of these g RNAs was assessed by a mitochondrial tetrazolium assay.RESULTS: All of g RNAs could significantly reduce HBs Ag or HBe Ag production in the culture supernatant, which was dependent on the region in which g RNA against. All of dual g RNAs could efficiently suppress HBs Ag and/or HBe Ag production for HBV of genotypes A-D, and the efficacy of dual g RNAs in suppressing HBs Ag and/or HBe Ag production was significantly increased when compared to the single g RNA used alone. Furthermore, by PCR direct sequencing we confirmed that these dual g RNAs could specifically destroy HBV expressing template by removing the fragment between the cleavage sites of the two used g RNAs. Most importantly, g RNA-5 and g RNA-12 combination not only could efficiently suppressing HBs Ag and/or HBe Ag production, but also destroy the ccc DNA reservoirs in Hep AD38 cells.CONCLUSION: These results suggested that CRISPR/Cas9 system could efficiently destroy HBV expressing templates(genotypes A-D) without apparent cytotoxicity. It may be a potential approach for eradication of persistent HBV ccc DNA in chronic HBV infection patients.展开更多
The central dogma of molecular biology states that the functions of RNA revolve around protein translation.Until the last decade,most researches were geared towards characterization of RNAs as intermediaries in protei...The central dogma of molecular biology states that the functions of RNA revolve around protein translation.Until the last decade,most researches were geared towards characterization of RNAs as intermediaries in protein translation,namely,messenger RNAs(mRNAs)as temporary copies of genetic information,ribosomal RNAs(rRNAs)as a main component of ribosome,or translators of codon sequence(t RNAs).The statistical reality,however,is that these processes account for less than 2%of the genome,and insufficiently explain the functionality of 98%of transcribed RNAs.Recent discoveries have unveiled thousands of unique non-coding RNAs(ncRNAs)and shifted the perception of them from being"junk"transcriptional products to"yet to be elucidated"—and potentially monumentally important—RNAs.Most ncRNAs are now known as key regulators in various networks in which they could lead to specific cellular responses and fates.In major cancers,ncRNAs have been identified as both oncogenic drivers and tumor suppressors,indicating a complex regulatory network among these ncRNAs.Herein,we provide a comprehensive review of the various ncRNAs and their functional roles in cancer,and the pre-clinical and clinical development of nc RNA-based therapeutics.A deeper understanding of ncRNAs could facilitate better design of personalized therapeutics.展开更多
As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous disea...As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast.While the risk factors associated with this cancer varies with respect to other cancers,genetic predisposition,most notably mutations in BRCA1 or BRCA2 gene,is an important causative factor for this malignancy.Breast cancers can begin in different areas of the breast,such as the ducts,the lobules,or the tissue in between.Within the large group of diverse breast carcinomas,there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites.It is important to distinguish between the various subtypes because they have different prognoses and treatment implications.As there are remarkable parallels between normal development and breast cancer progression at the molecular level,it has been postulated that breast cancer may be derived from mammary cancer stem cells.Normal breast development and mammary stem cells are regulated by several signaling pathways,such as estrogen receptors(ERs),HER2,and Wnt/b-catenin signaling pathways,which control stem cell proliferation,cell death,cell differentiation,and cell motility.Furthermore,emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer,especially for triple-negative breast cancer.This review provides a comprehensive survey of the molecular,cellular and genetic aspects of breast cancer.展开更多
Objective： To identify differentially expressed long non-coding RNAs （lncRNAs） involved in the metastasis of epithelial ovarian cancer. Methods： An in vitro invasion assay was performed to validate the invasive ca...Objective： To identify differentially expressed long non-coding RNAs （lncRNAs） involved in the metastasis of epithelial ovarian cancer. Methods： An in vitro invasion assay was performed to validate the invasive capability of SKOV3 and SKOV3.ip1 cell lines. Total R.NA was then extracted, and microarray analysis was performed. Moreover, nine lncRNAs were selected for validation using RT-qPCR. Results： Compared with the SKOV3 cells, the SKOV3.ip1 cells significantly improved in the in vitro invasive activity. Of the 4,956 lncRNAs detected in the microarra~ 583 and 578 lncRNAs were upregulated and downregulated, respectivel~ in SKOV3.ip1 cells, compared with the parental SKOV3 cells. Seven of the analyzed lncRNAs （MALAT1, H19, UCA1, CCAT1, LOC645249, LOC100128881, and LOC100292680） confirmed the deregulation found by microarray analysis. Conclusion： LncRNAs clusters were differentially expressed in ovarian cancer cells with varying metastatic potentials. This result indicates that some lncRNAs might exert a partial or key role in epithelial ovarian cancer metastasis. Further studies should be conducted to determine the roles of these lncRNAs in ovarian cancer metastasis.展开更多
Noncoding RNAs(nc RNAs) have attracted much attention in cancer research field. They are involved in cellular development, proliferation, differentiation and apoptosis. The dysregulation of nc RNAs has been reported i...Noncoding RNAs(nc RNAs) have attracted much attention in cancer research field. They are involved in cellular development, proliferation, differentiation and apoptosis. The dysregulation of nc RNAs has been reported in tumor initiation, progression, invasion and metastasis in various cancers, including gastric cancer(GC). In the past few years, an accumulating body of evidence has deepened our understanding of nc RNAs, and several emerging nc RNAs have been identified, such as PIWI-interacting RNAs(pi RNAs) and circular RNAs(circ RNAs). The competing endogenous RNA(ce RNA) networks include m RNAs, micro RNAs, long nc RNAs(lnc RNAs) and circ RNAs, which play critical roles in the tumorigenesis of GC. This review summarizes the recent hotspots of nc RNAs involved in GC pathobiology and their potential applications in GC. Finally, we briefly discuss the advances in the ce RNA network in GC.展开更多
Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and ...Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.展开更多
Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer rese...Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer research. To date,the roles of mi RNAs and lnc RNAs have been extensively studied in GC,suggesting that mi RNAs and lnc RNAs represent a vital component of tumor biology. Furthermore,circulating mi RNAs and lnc RNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating mi RNAs and lnc RNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for mi RNA secretion have been elucidated,including active secretion by microvesicles,exosomes,apoptotic bodies,highdensity lipoproteins and protein complexes as well as passive leakage from cells. However,the mechanism underlying lnc RNA secretion and the functions of circulating mi RNAs and lnc RNAs have not been fully illuminated. Concurrently,to standardize results of global investigations of circulating mi RNAs and lnc RNAs biomarker studies,several recommendations for preanalytic considerations are put forward. In this review,we summarize the known circulating mi RNAs and lnc RNAs for GC diagnosis. The possible mechanism of mi RNA and lnc RNA secretion as well as methodologies for identification of circulating mi RNAs and lnc RNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening.展开更多
Micro RNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Aberrant ...Micro RNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Aberrant expression of mi RNAs is an important factor in the development and progression of disease. The canonical myomi Rs(mi R-1,-133 and-206) are central to the development and health of mammalian skeletal and cardiac muscles, but new findings show they have regulatory roles in the development of other mammalian non-muscle tissues, including nerve, brain structures, adipose and some specialised immunological cells. Moreover, the deregulation of myomi R expression is associated with a variety of different cancers, where typically they have tumor suppressor functions, although examples of an oncogenic role illustrate their diverse function in different cell environments. This review examines the involvement of the related myomi Rs at the crossroads between cell development/tissue regeneration/tissue inflammation responses, and cancer development.展开更多
Ginsenosides are a series of glycosylated triterpenoids which belong to protopanaxadiol(PPD)-,protopanaxatriol(PPT)-,ocotillol(OCT)-and oleanane(OA)-type saponins known as active compounds of Panax genus.They are accu...Ginsenosides are a series of glycosylated triterpenoids which belong to protopanaxadiol(PPD)-,protopanaxatriol(PPT)-,ocotillol(OCT)-and oleanane(OA)-type saponins known as active compounds of Panax genus.They are accumulated in plant roots,stems,leaves,and flowers.The content and composition of ginsenosides are varied in different ginseng species,and in different parts of a certain plant.In this review,we summarized the representative saponins structures,their distributions and the contents in nearly 20 Panax species,and updated the biosynthetic pathways of ginsenosides focusing on enzymes responsible for structural diversified ginsenoside biosynthesis.We also emphasized the transcription factors in ginsenoside biosynthesis and non-coding RNAs in the growth of Panax genus plants,and highlighted the current three major biotechnological applications for ginsenosides production.This review covered advances in the past four decades,providing more clues for chemical discrimination and assessment on certain ginseng plants,new perspectives for rational evaluation and utilization of ginseng resource,and potential strategies for production of specific ginsenosides.展开更多
Hepatocellular carcinoma(HCC) is an aggressive malignancy and the second leading cause of cancerrelated deaths worldwide. Conventional biomarkers exhibit poor performance in the surveillance,diagnosis,and prognosis of...Hepatocellular carcinoma(HCC) is an aggressive malignancy and the second leading cause of cancerrelated deaths worldwide. Conventional biomarkers exhibit poor performance in the surveillance,diagnosis,and prognosis of HCC. Micro RNAs(mi RNAs) are a class of evolutionarily conserved small non-coding RNAs that are involved in the regulation of gene expression and protein translation,and they play critical roles in cell growth,differentiation,and the development of various types of cancers,including HCC. Recent evidence revealed the role of mi RNAs as potential novel and ideal biomarkers for HCC. mi RNAs are released to extracellular spaces,and they are extremely stable in bodily fluids,including serum or plasma,where they are packaged into various microparticles or associated with RNA-binding proteins. Numerous studies have demonstrated that circulating mi RNAs have potential applications as minimally invasive biomarkers for HCC diagnosis and prognosis. The present review highlights current understanding of mi RNA biogenesis and the origins and types of circulating mi RNAs. We summarize recent progress in the use of circulating mi RNAs as diagnostic and prognostic biomarkers for HCC. We also discuss the challenges and perspectives of the clinical utility of circulating mi RNAs in HCC.展开更多
Pharmacokinetics(PK)is the study of the absorption,distribution,metabolism,and excretion(ADME)processes of a drug.Understanding PK properties is essential for drug development and precision medication.In this review w...Pharmacokinetics(PK)is the study of the absorption,distribution,metabolism,and excretion(ADME)processes of a drug.Understanding PK properties is essential for drug development and precision medication.In this review we provided an overview of recent research on PK with focus on the following aspects:(1)an update on drug-metabolizing enzymes and transporters in the determination of PK,as well as advances in xenobiotic receptors and noncoding RNAs(ncRNAs)in the modulation of PK,providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy;(2)current status and trends in assessing drug-drug interactions,especially interactions between drugs and herbs,between drugs and therapeutic biologies,and microbiota-mediated interactions:(3)advances in understanding the effects of diseases on PK,particularly changes in metabolizing enzymes and transporters with disease progression;(4)trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies:(5)emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes,especially non-P450s.Existing challenges and perspectives on future directions are discussed,and may stimulate the development of new research models,technologies,and strategies towards the development of better drugs and improved clinical practice.展开更多
AIM: To profile expression of microRNAs (miRNAs) in gastric cancer cells and investigate the effect of miR-374b-5p on gastric cancer cell invasion and metastasis.
MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of ...MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of cellular activity, including differentiation and development, metabolism, proliferation, apoptotic cell death, viral infection and tumorigenesis. Recent studies provide clear evidence that miRNAs are abundant in the liver and modulate a diverse spectrum of liver functions. Deregulation of miRNA expression may be a key pathogenetic factor in many liver diseases including viral hepatitis, hepatocellular cancer and polycystic liver diseases. A clearer understanding of the mechanisms involved in miRNA deregulation will offer new diagnostic and therapeutic strategies to treat liver diseases. Moreover, better understanding of miRNA regulation and identification of tissue-specific miRNA targets employing transgenic/knockout models and/or modulating oligonucleotides will improve our knowledge of liver physiology and diseases.展开更多
Oral squamous cell carcinoma(OSCC),the eighth most prevalent cancer in the world,arises from the interaction of multiple factors including tobacco,alcohol consumption,and betel quid.Chemotherapeutic agents such as cis...Oral squamous cell carcinoma(OSCC),the eighth most prevalent cancer in the world,arises from the interaction of multiple factors including tobacco,alcohol consumption,and betel quid.Chemotherapeutic agents such as cisplatin,5-fluorouracil,and paclitaxel have now become the first-line options for OSCC patients.Nevertheless,most OSCC patients eventually acquire drug resistance,leading to poor prognosis.With the discovery and identification of non-coding RNAs(ncRNAs),the functions of dysregulated ncRNAs in OSCC development and drug resistance are gradually being widely recognized.The mechanisms of drug resistance of OSCC are intricate and involve drug efflux,epithelial-mesenchymal transition,DNA damage repair,and autophagy.At present,strategies to explore the reversal of drug resistance of OSCC need to be urgently developed.Nano-delivery and self-cellular drug delivery platforms are considered as effective strategies to overcome drug resistance due to their tumor targeting,controlled release,and consistent pharmacokinetic profiles.In particular,the combined application of new technologies(including CRISPR systems)opened up new horizons for the treatment of drug resistance of OSCC.Hence,this review explored emerging regulatory functions of ncRNAs in drug resistance of OSCC,elucidated multiple ncRNA-meditated mechanisms of drug resistance of OSCC,and discussed the potential value of drug delivery platforms using nanoparticles and self-cells as carriers in drug resistance of OSCC.展开更多
Development of tools for targeted modifications of specific DNA sequences in plants is of great importance to basic plant biology research as well as crop improvement.The ability to cut DNA at specific locations in th...Development of tools for targeted modifications of specific DNA sequences in plants is of great importance to basic plant biology research as well as crop improvement.The ability to cut DNA at specific locations in the genome to generate doublestrand breaks（DSBs）in vivo is a prerequisite for any genome editing efforts.展开更多
Objective:Evidence suggests that various diseases may contribute to the circular RNAs (circRNAs) expression disorder. This review was aimed at looking for appropriate biomarkers for the treatment of diseases.Data sour...Objective:Evidence suggests that various diseases may contribute to the circular RNAs (circRNAs) expression disorder. This review was aimed at looking for appropriate biomarkers for the treatment of diseases.Data sources:The comprehensive search used online literature databases including PubMed of National Center for Biotechnology Information and Web of Science.Study selection:The study selection was based on the following keywords: circRNAs, biogenesis, biologic function, and disease. The time limit for literature retrieval was from the year 1976 to 2019, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type.Results:CircRNAs are one of the critical non-coding RNAs (ncRNAs), which are covalently closed continuous loops that do not possess 5' and 3' ends. This makes them resistant to exoribonuclease activity and potentially more stable than their cognate linear transcripts, thus making them ideal candidates for biomarker development. Due to the stable and extensive tissue-specific expression of circRNAs, they can function as microRNA sponges and bind to RNA-binding proteins, regulate transcription and splicing, and translate into proteins to participate in the regulation of physiologic and pathologic processes. Moreover, the expression disorders of circRNAs in diseases, such as neurodegenerative disease, cardiovascular disease, and cancer, make them have potential applications for the diagnosis and treatment of diseases.Conclusions:Changes in circRNA expression profiles related to various diseases, and circRNAs often exhibit low expression in cancer tissues. In addition, circRNAs can be detected in patient’s body fluids to indicate that circRNAs are effective biomarkers for disease diagnosis. These characteristics make circRNAs have potential applications as novel therapeutic targets for diseases.展开更多
基金supported by the National Basic Research Program of China(2010CB912801,2013CB910801)National High Technology Research and Development Program of China(2012AA022501)National Natural Science Foundation of China(31070702,31270836)
文摘Long non-coding RNAs(lncRNAs),which represent a new frontier in molecular biology,play important roles in regulating gene expression at epigenetic,transcriptional and post-transcriptional levels.More and more lncRNAs have been found to play important roles in normal cell physiological activities,and participate in the development of varieties of tumors and other diseases.Previously,we have only been able to determine the function of lncRNAs through multiple mechanisms,including genetic imprinting,chromatin remodeling,splicing regulation,mRNA decay,and translational regulation.Application of technological advances to research into the function of lncRNAs is extremely important.The major tools for exploring lncRNAs include microarrays,RNA sequencing(RNA-seq),Northern blotting,real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR),fluorescence in situ hybridization(FISH),RNA interference(RNAi),RNA-binding protein immunoprecipitation(RIP),chromatin isolation by RNA purification(ChIRP),crosslinking-immunopurification(CLIP),and bioinformatic prediction.In this review,we highlight the functions of lncRNAs,and advanced methods to research lncRNA-protein interactions.
基金Supported by Natural Science Foundation of China,No.81471938the National S and T Major Project for Infectious Diseases,No.2013ZX10002-002 and No.2012ZX10002-005111 Project,No.B07001
文摘AIM: To screen and investigate the effective g RNAs against hepatitis B virus(HBV) of genotypes A-D.METHODS: A total of 15 g RNAs against HBV of genotypes A-D were designed. Eleven combinations of two above g RNAs(dual-g RNAs) covering the regulatory region of HBV were chosen. The efficiency of each g RNA and 11 dual-g RNAs on the suppression of HBV(genotypes A-D) replication was examined by the measurement of HBV surface antigen(HBs Ag) or e antigen(HBe Ag) in the culture supernatant. The destruction of HBV-expressing vector was examined in Hu H7 cells co-transfected with dual-g RNAs and HBVexpressing vector using polymerase chain reaction(PCR) and sequencing method, and the destruction of ccc DNAwas examined in Hep AD38 cells using KCl precipitation, plasmid-safe ATP-dependent DNase(PSAD) digestion, rolling circle amplification and quantitative PCR combined method. The cytotoxicity of these g RNAs was assessed by a mitochondrial tetrazolium assay.RESULTS: All of g RNAs could significantly reduce HBs Ag or HBe Ag production in the culture supernatant, which was dependent on the region in which g RNA against. All of dual g RNAs could efficiently suppress HBs Ag and/or HBe Ag production for HBV of genotypes A-D, and the efficacy of dual g RNAs in suppressing HBs Ag and/or HBe Ag production was significantly increased when compared to the single g RNA used alone. Furthermore, by PCR direct sequencing we confirmed that these dual g RNAs could specifically destroy HBV expressing template by removing the fragment between the cleavage sites of the two used g RNAs. Most importantly, g RNA-5 and g RNA-12 combination not only could efficiently suppressing HBs Ag and/or HBe Ag production, but also destroy the ccc DNA reservoirs in Hep AD38 cells.CONCLUSION: These results suggested that CRISPR/Cas9 system could efficiently destroy HBV expressing templates(genotypes A-D) without apparent cytotoxicity. It may be a potential approach for eradication of persistent HBV ccc DNA in chronic HBV infection patients.
基金supported by grants from the National Key Research and Development Program of China(2016YFC1302300)the National Natural Science Foundation of China(81621004,81720108029,81930081,91940305,81874226 and 81803020)+2 种基金Guangdong Science and Technology Department(2017B030314026)Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201001)Guangzhou Science Technology and Innovation Commission(201803040015)partly supported by Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation。
文摘The central dogma of molecular biology states that the functions of RNA revolve around protein translation.Until the last decade,most researches were geared towards characterization of RNAs as intermediaries in protein translation,namely,messenger RNAs(mRNAs)as temporary copies of genetic information,ribosomal RNAs(rRNAs)as a main component of ribosome,or translators of codon sequence(t RNAs).The statistical reality,however,is that these processes account for less than 2%of the genome,and insufficiently explain the functionality of 98%of transcribed RNAs.Recent discoveries have unveiled thousands of unique non-coding RNAs(ncRNAs)and shifted the perception of them from being"junk"transcriptional products to"yet to be elucidated"—and potentially monumentally important—RNAs.Most ncRNAs are now known as key regulators in various networks in which they could lead to specific cellular responses and fates.In major cancers,ncRNAs have been identified as both oncogenic drivers and tumor suppressors,indicating a complex regulatory network among these ncRNAs.Herein,we provide a comprehensive review of the various ncRNAs and their functional roles in cancer,and the pre-clinical and clinical development of nc RNA-based therapeutics.A deeper understanding of ncRNAs could facilitate better design of personalized therapeutics.
基金Research in the authors’laboratories was supported in part by research grants from the National Institutes of Health(CA226303 to TCH)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906 to TCH)the Natural Science Foundation of China(#30670811,#31171243,and#31420103915 to GR).
文摘As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast.While the risk factors associated with this cancer varies with respect to other cancers,genetic predisposition,most notably mutations in BRCA1 or BRCA2 gene,is an important causative factor for this malignancy.Breast cancers can begin in different areas of the breast,such as the ducts,the lobules,or the tissue in between.Within the large group of diverse breast carcinomas,there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites.It is important to distinguish between the various subtypes because they have different prognoses and treatment implications.As there are remarkable parallels between normal development and breast cancer progression at the molecular level,it has been postulated that breast cancer may be derived from mammary cancer stem cells.Normal breast development and mammary stem cells are regulated by several signaling pathways,such as estrogen receptors(ERs),HER2,and Wnt/b-catenin signaling pathways,which control stem cell proliferation,cell death,cell differentiation,and cell motility.Furthermore,emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer,especially for triple-negative breast cancer.This review provides a comprehensive survey of the molecular,cellular and genetic aspects of breast cancer.
文摘Objective： To identify differentially expressed long non-coding RNAs （lncRNAs） involved in the metastasis of epithelial ovarian cancer. Methods： An in vitro invasion assay was performed to validate the invasive capability of SKOV3 and SKOV3.ip1 cell lines. Total R.NA was then extracted, and microarray analysis was performed. Moreover, nine lncRNAs were selected for validation using RT-qPCR. Results： Compared with the SKOV3 cells, the SKOV3.ip1 cells significantly improved in the in vitro invasive activity. Of the 4,956 lncRNAs detected in the microarra~ 583 and 578 lncRNAs were upregulated and downregulated, respectivel~ in SKOV3.ip1 cells, compared with the parental SKOV3 cells. Seven of the analyzed lncRNAs （MALAT1, H19, UCA1, CCAT1, LOC645249, LOC100128881, and LOC100292680） confirmed the deregulation found by microarray analysis. Conclusion： LncRNAs clusters were differentially expressed in ovarian cancer cells with varying metastatic potentials. This result indicates that some lncRNAs might exert a partial or key role in epithelial ovarian cancer metastasis. Further studies should be conducted to determine the roles of these lncRNAs in ovarian cancer metastasis.
基金Supported by National Natural Science Foundation of China,No.81472220Shanghai Science and Technology Development Fund,Domestic Science and Technology Cooperation Project,No.14495800300
文摘Noncoding RNAs(nc RNAs) have attracted much attention in cancer research field. They are involved in cellular development, proliferation, differentiation and apoptosis. The dysregulation of nc RNAs has been reported in tumor initiation, progression, invasion and metastasis in various cancers, including gastric cancer(GC). In the past few years, an accumulating body of evidence has deepened our understanding of nc RNAs, and several emerging nc RNAs have been identified, such as PIWI-interacting RNAs(pi RNAs) and circular RNAs(circ RNAs). The competing endogenous RNA(ce RNA) networks include m RNAs, micro RNAs, long nc RNAs(lnc RNAs) and circ RNAs, which play critical roles in the tumorigenesis of GC. This review summarizes the recent hotspots of nc RNAs involved in GC pathobiology and their potential applications in GC. Finally, we briefly discuss the advances in the ce RNA network in GC.
基金Supported by the National Research,Development and Innovation Office,No.NVKP_16-1-2016-0004
文摘Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.
文摘Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer research. To date,the roles of mi RNAs and lnc RNAs have been extensively studied in GC,suggesting that mi RNAs and lnc RNAs represent a vital component of tumor biology. Furthermore,circulating mi RNAs and lnc RNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating mi RNAs and lnc RNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for mi RNA secretion have been elucidated,including active secretion by microvesicles,exosomes,apoptotic bodies,highdensity lipoproteins and protein complexes as well as passive leakage from cells. However,the mechanism underlying lnc RNA secretion and the functions of circulating mi RNAs and lnc RNAs have not been fully illuminated. Concurrently,to standardize results of global investigations of circulating mi RNAs and lnc RNAs biomarker studies,several recommendations for preanalytic considerations are put forward. In this review,we summarize the known circulating mi RNAs and lnc RNAs for GC diagnosis. The possible mechanism of mi RNA and lnc RNA secretion as well as methodologies for identification of circulating mi RNAs and lnc RNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening.
基金Supported by National High-tech Program of China,Nos.2006AA020701 and 2009AA022701
文摘Micro RNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Aberrant expression of mi RNAs is an important factor in the development and progression of disease. The canonical myomi Rs(mi R-1,-133 and-206) are central to the development and health of mammalian skeletal and cardiac muscles, but new findings show they have regulatory roles in the development of other mammalian non-muscle tissues, including nerve, brain structures, adipose and some specialised immunological cells. Moreover, the deregulation of myomi R expression is associated with a variety of different cancers, where typically they have tumor suppressor functions, although examples of an oncogenic role illustrate their diverse function in different cell environments. This review examines the involvement of the related myomi Rs at the crossroads between cell development/tissue regeneration/tissue inflammation responses, and cancer development.
基金supported by National Natural Science Foundation of China(No.81673540,No.81530096)Natural Science Foundation of Shanghai(No.16ZR1434100,China)Shanghai local Science and Technology Development Fund Program guided by the Central Government(YDZX20203100002948,China)
文摘Ginsenosides are a series of glycosylated triterpenoids which belong to protopanaxadiol(PPD)-,protopanaxatriol(PPT)-,ocotillol(OCT)-and oleanane(OA)-type saponins known as active compounds of Panax genus.They are accumulated in plant roots,stems,leaves,and flowers.The content and composition of ginsenosides are varied in different ginseng species,and in different parts of a certain plant.In this review,we summarized the representative saponins structures,their distributions and the contents in nearly 20 Panax species,and updated the biosynthetic pathways of ginsenosides focusing on enzymes responsible for structural diversified ginsenoside biosynthesis.We also emphasized the transcription factors in ginsenoside biosynthesis and non-coding RNAs in the growth of Panax genus plants,and highlighted the current three major biotechnological applications for ginsenosides production.This review covered advances in the past four decades,providing more clues for chemical discrimination and assessment on certain ginseng plants,new perspectives for rational evaluation and utilization of ginseng resource,and potential strategies for production of specific ginsenosides.
基金Supported by Department of Public Health of Jilin Province of China,No.2009Z080 and No.2014Q025Supporting Program of Bethune Medical Research of Jilin University,No.2013207058
文摘Hepatocellular carcinoma(HCC) is an aggressive malignancy and the second leading cause of cancerrelated deaths worldwide. Conventional biomarkers exhibit poor performance in the surveillance,diagnosis,and prognosis of HCC. Micro RNAs(mi RNAs) are a class of evolutionarily conserved small non-coding RNAs that are involved in the regulation of gene expression and protein translation,and they play critical roles in cell growth,differentiation,and the development of various types of cancers,including HCC. Recent evidence revealed the role of mi RNAs as potential novel and ideal biomarkers for HCC. mi RNAs are released to extracellular spaces,and they are extremely stable in bodily fluids,including serum or plasma,where they are packaged into various microparticles or associated with RNA-binding proteins. Numerous studies have demonstrated that circulating mi RNAs have potential applications as minimally invasive biomarkers for HCC diagnosis and prognosis. The present review highlights current understanding of mi RNA biogenesis and the origins and types of circulating mi RNAs. We summarize recent progress in the use of circulating mi RNAs as diagnostic and prognostic biomarkers for HCC. We also discuss the challenges and perspectives of the clinical utility of circulating mi RNAs in HCC.
基金supported by National Natural Science Foundation of China(grants:81573489,81522047,81730103,81320108027,81660618,and 81773808)the National Key Research and Development Program(grant:2017YFE0109900 and 2017YFC0909303,China)+5 种基金the 111 project(grant:B16047,China)the Key Laboratory Foundation of Guangdong Province(grant:2017B030314030,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y093,China)National Engineering and Technology Research Center for New drug Druggability Evaluation(Seed Program of Guangdong Province,2017B090903004,China)Natural Science Foundation of Guangdong(grant:2017A030311018 and 2015A030313124,China)National Institutes of Health(grants No.R01CA225958 and R01GM113888 to Ai-Ming Yu,USA).
文摘Pharmacokinetics(PK)is the study of the absorption,distribution,metabolism,and excretion(ADME)processes of a drug.Understanding PK properties is essential for drug development and precision medication.In this review we provided an overview of recent research on PK with focus on the following aspects:(1)an update on drug-metabolizing enzymes and transporters in the determination of PK,as well as advances in xenobiotic receptors and noncoding RNAs(ncRNAs)in the modulation of PK,providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy;(2)current status and trends in assessing drug-drug interactions,especially interactions between drugs and herbs,between drugs and therapeutic biologies,and microbiota-mediated interactions:(3)advances in understanding the effects of diseases on PK,particularly changes in metabolizing enzymes and transporters with disease progression;(4)trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies:(5)emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes,especially non-P450s.Existing challenges and perspectives on future directions are discussed,and may stimulate the development of new research models,technologies,and strategies towards the development of better drugs and improved clinical practice.
基金Supported by National Natural Science Foundation of China,No.81071965
文摘AIM: To profile expression of microRNAs (miRNAs) in gastric cancer cells and investigate the effect of miR-374b-5p on gastric cancer cell invasion and metastasis.
基金Supported by National Institute of Health grant (R01 AI071321)the Tobacco Settlement Foundation of Nebraska (LB 692)
文摘MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of cellular activity, including differentiation and development, metabolism, proliferation, apoptotic cell death, viral infection and tumorigenesis. Recent studies provide clear evidence that miRNAs are abundant in the liver and modulate a diverse spectrum of liver functions. Deregulation of miRNA expression may be a key pathogenetic factor in many liver diseases including viral hepatitis, hepatocellular cancer and polycystic liver diseases. A clearer understanding of the mechanisms involved in miRNA deregulation will offer new diagnostic and therapeutic strategies to treat liver diseases. Moreover, better understanding of miRNA regulation and identification of tissue-specific miRNA targets employing transgenic/knockout models and/or modulating oligonucleotides will improve our knowledge of liver physiology and diseases.
基金National Natural Science Foundation of China,Grant/Award Number:81700522Natural Science Foundation of Anhui Province,Grant/Award Numbers:1808085MH235,1908085QH328Grants for ScientificResearch of BSKY from Anhui Medical University,Grant/Award Number:XJ201706。
文摘Oral squamous cell carcinoma(OSCC),the eighth most prevalent cancer in the world,arises from the interaction of multiple factors including tobacco,alcohol consumption,and betel quid.Chemotherapeutic agents such as cisplatin,5-fluorouracil,and paclitaxel have now become the first-line options for OSCC patients.Nevertheless,most OSCC patients eventually acquire drug resistance,leading to poor prognosis.With the discovery and identification of non-coding RNAs(ncRNAs),the functions of dysregulated ncRNAs in OSCC development and drug resistance are gradually being widely recognized.The mechanisms of drug resistance of OSCC are intricate and involve drug efflux,epithelial-mesenchymal transition,DNA damage repair,and autophagy.At present,strategies to explore the reversal of drug resistance of OSCC need to be urgently developed.Nano-delivery and self-cellular drug delivery platforms are considered as effective strategies to overcome drug resistance due to their tumor targeting,controlled release,and consistent pharmacokinetic profiles.In particular,the combined application of new technologies(including CRISPR systems)opened up new horizons for the treatment of drug resistance of OSCC.Hence,this review explored emerging regulatory functions of ncRNAs in drug resistance of OSCC,elucidated multiple ncRNA-meditated mechanisms of drug resistance of OSCC,and discussed the potential value of drug delivery platforms using nanoparticles and self-cells as carriers in drug resistance of OSCC.
基金supported by a National Transgenic Science and Technology Program (2016ZX08010002)to R.W.a startup fund from the Huazhong Agricultural University
文摘Development of tools for targeted modifications of specific DNA sequences in plants is of great importance to basic plant biology research as well as crop improvement.The ability to cut DNA at specific locations in the genome to generate doublestrand breaks（DSBs）in vivo is a prerequisite for any genome editing efforts.
文摘Objective:Evidence suggests that various diseases may contribute to the circular RNAs (circRNAs) expression disorder. This review was aimed at looking for appropriate biomarkers for the treatment of diseases.Data sources:The comprehensive search used online literature databases including PubMed of National Center for Biotechnology Information and Web of Science.Study selection:The study selection was based on the following keywords: circRNAs, biogenesis, biologic function, and disease. The time limit for literature retrieval was from the year 1976 to 2019, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type.Results:CircRNAs are one of the critical non-coding RNAs (ncRNAs), which are covalently closed continuous loops that do not possess 5' and 3' ends. This makes them resistant to exoribonuclease activity and potentially more stable than their cognate linear transcripts, thus making them ideal candidates for biomarker development. Due to the stable and extensive tissue-specific expression of circRNAs, they can function as microRNA sponges and bind to RNA-binding proteins, regulate transcription and splicing, and translate into proteins to participate in the regulation of physiologic and pathologic processes. Moreover, the expression disorders of circRNAs in diseases, such as neurodegenerative disease, cardiovascular disease, and cancer, make them have potential applications for the diagnosis and treatment of diseases.Conclusions:Changes in circRNA expression profiles related to various diseases, and circRNAs often exhibit low expression in cancer tissues. In addition, circRNAs can be detected in patient’s body fluids to indicate that circRNAs are effective biomarkers for disease diagnosis. These characteristics make circRNAs have potential applications as novel therapeutic targets for diseases.
