Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome ap...Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA （lncRNA）, a heteroge- neous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA （miRNA） pathways, lncRNA has been shown to act as both a source and an inhi- bitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying com- plexes by directing them to specific loci.展开更多
Seventy-five previously known plant microRNAs (miRNAs) were classified into 14 families according to their gene sequence identity. A total of 18,694 plant expressed sequence tags (EST) were found in the GenBank EST da...Seventy-five previously known plant microRNAs (miRNAs) were classified into 14 families according to their gene sequence identity. A total of 18,694 plant expressed sequence tags (EST) were found in the GenBank EST databases by comparing all previously known Arabidopsis miRNAs to GenBank’s plant EST databases with BLAST algorithms. After removing the EST sequences with high numbers (more than 2) of mismatched nucleotides, a total of 812 EST contigs were identified. After predicting and scoring the RNA secondary structure of the 812 EST sequences using mFold software, 338 new potential miRNAs were identified in 60 plant species. miRNAs are widespread. Some microRNAs may highly conserve in the plant kingdom, and they may have the same ancestor in very early evolution. There is no nucleotide substitution in most miRNAs among many plant species. Some of the new identified potential miRNAs may be induced and regulated by environmental biotic and abiotic stresses. Some may be preferentially expressed in specific tissues, and are regulated by developmental switching. These findings suggest that EST analysis is a good alternative strategy for identifying new miRNA candidates, their targets, and other genes. A large number of miRNAs exist in different plant species and play important roles in plant developmental switching and plant responses to environmental abiotic and biotic stresses as well as signal transduction. Environmental stresses and developmental switching may be the signals for synthesis and regulation of miRNAs in plants. A model for miRNA induction and expression, and gene regulation by miRNA is hypothesized.展开更多
Gastric cancer is one of the leading causes of cancer mortality in the world. Aberrant expression of microRNAs (miRNAs) is the hallmark of this disease. MiRNAs are endogenous non-coding RNAs that are involved in many ...Gastric cancer is one of the leading causes of cancer mortality in the world. Aberrant expression of microRNAs (miRNAs) is the hallmark of this disease. MiRNAs are endogenous non-coding RNAs that are involved in many biological processes (e.g., cell proliferation, differentiation, apoptosis, invasion and development) through gene repression. Deregulation of miRNA expression in gastric tumors and cancer cell lines have been documented to contribute in tumorigenesis, and the expression signature may correlate with different cancer types and clinicopathological features. Here, we summarized the updated gastric cancer-associated miRNAs and the downstream targets in the process of tumorigenesis. Recently, many researchers make use of the miRNA microarray platform to profile miRNA expression in gastric cancer and correlated with different clinical parameters. Its application on cancer diagnosis, prognosis and predicting treatment response rate are still underway and needs further investigation. Emerging roles of miRNAs with oncogenic or tumor suppressive properties in gastric tumorigenesis were discussed. Epigenetic silencing of miRNA by hypermethylation of promoter CpG island was also observed in gastric cancer. However, detailed mechanisms of how miRNAs regulate gene expression in gastric cancer has not been well studied. In this review, we highlight the up-to-date findings on the deregulated miRNAs in gastric cancer, and the potential use of miRNA in the clinical settings, such as diagnostic/prognostic markers and chemotherapeutic tools.展开更多
Studies have shown cell-free microRNA(miRNA) circulating in the serum and plasma with specific expression in cancer,indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy.This study wa...Studies have shown cell-free microRNA(miRNA) circulating in the serum and plasma with specific expression in cancer,indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy.This study was to investigate whether plasma miRNA-21(miR-21) can be used as a biomarker for the early detection of non-small cell lung cancer(NSCLC) and to explore its association with clinicopathologic features and sensitivity to platinum-based chemotherapy.We used real-time RT-PCR to investigate the expression of miR-21 in the plasma of 63 NSCLC patients and 30 healthy controls and correlated the findings with early diagnosis,pathologic parameters,and treatment.Thirty-five patients(stages IIIB and IV) were evaluable for chemotherapeutic responses:11 had partial response(PR);24 had stable and progressive disease(SD+PD).Plasma miR-21 was significantly higher in NSCLC patients than in age-and sex-matched controls(P<0.001).miR-21 was related to TNM stage(P<0.001),but not related to age,sex,smoking status,histological classification,lymph node status,and metastasis(all P>0.05).This marker yielded a receiver operating characteristic(ROC) curve area of 0.775(95% CI:0.681-0.868) with 76.2% sensitivity and 70.0% specificity.Importantly,miR-21 plasma levels in PR samples were several folds lower than that in SD plus PD samples(P=0.049),and were close to that in healthy controls(P=0.130).Plasma miR-21 can serve as a circulating tumor biomarker for the early diagnosis of NSCLC and is related to the sensitivity to platinum-base chemotherapy.展开更多
Epithelial-to-mesenchymal transition(EMT)is implicated in a wide array of malignant behaviors of cancers,including proliferation,invasion,and metastasis.Most notably,previou studies have indicated that both cancer ste...Epithelial-to-mesenchymal transition(EMT)is implicated in a wide array of malignant behaviors of cancers,including proliferation,invasion,and metastasis.Most notably,previou studies have indicated that both cancer stem-like properties and drug resistance were associated with EMT.Furthermore,microRNAs(miRNAs)play a pivotal role in the regulation of EMT phenotype,as a result,some miRNAs impact cancer stemness and drug resistance.Therefore,understanding the relationship between EMT-associated miRNAs and cancer stemness/drug resistance is beneficial to both basic research and clinical treatment.In this review,we preliminarily looked into the various roles that the EMT-associated miRNAs play in the stem-like nature of malignant cells.Then,we reviewed the interaction between EMT-associated miRNAs and the drugresistant complex signaling pathways of multiple cancers including lung cancer,gastric cancer,gynecologic cancer,breast cancer,liver cancer,colorectal cancer,pancreatic cancer,esophageal cancer,and nasopharyngeal cancer.We finally discussed the relationship between EMT,cancer stemness,and drug resistance,as well as looked forward to the potential applications of miRNA therapy for malignant tumors.展开更多
MicroRNAs(miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and patholog...MicroRNAs(miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathological processes, such as development, cell differentiation, proliferation, apoptosis and tumor growth. miRNAs work as small guide molecules in RNA silencing, by negatively regulating the expression of several genes both at mRNA and protein level, by degrading their mRNA target and/or by silencing translation. One of the most recent advances in the field is the comprehension of their role in oncogenesis. The number of miRNA genes is increasing and an alteration in the level of miRNAs is involved in the initiation, progression and metastases formation of several tumors. Some tumor types show a distinct miRNA signature that distinguishes them from normal tissues and from other cancer types. Genetic and biochemical evidence supports the essential role of miRNAs in tumor development. Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the cause of this dysregulation is still unknown. Here, we discuss the biogenesis of miRNAs, focusing on the mechanisms by which they regulate protein synthesis. In addition we debate on their role in cancer, highlighting their potential to become therapeutic targets.展开更多
Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) play...Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4 (TLR4) complex in LPS recognition and the importance of the TLR4-induced signaling pathways are evaluated in ALD.展开更多
Emerging evidence has shown the association of aberrantly expressed microRNAs （miRNAs） with tumor development and progression. However, little is known about the potential role of miRNAs in gastric carcinogenesis. H...Emerging evidence has shown the association of aberrantly expressed microRNAs （miRNAs） with tumor development and progression. However, little is known about the potential role of miRNAs in gastric carcinogenesis. Here, we performed miRNA microarray to screen miRNAs differentially expressed in the paired gastric cancer and their adjacent nontumor tissues and found that miR-375 was greatly downregulated in gastric cancer tissues. Quantitative real-time PCR analysis verified that miR-375 expression was significantly decreased in more than 90% of primary gastric cancers compared with their nontumor counterparts from patients undergoing gastric resection. Overexpression of miR-375 significantly inhibited gastric cancer cell proliferation in vitro and in vivo. Forced expression of miR-375 in gastric cancer cells significantly reduced the protein level of Janus kinase 2 （JAK2） and repressed the activity of a luciferase reporter carrying the 3＇-untranslated region of JAK2, which was abolished by mutation of the predicted miR-375-binding site, indicating that JAK2 may be a miR-375 target gene. Either inhibition of JAK2 activity by AG490 or silencing of JAK2 by RNAi suppressed gastric cancer cell proliferation resembling that of miR-375 overexpression. Moreover, ectopic expression of JAK2 can partially reverse the inhibition of cell proliferation caused by miR-375. Finally, we found a significant inverse correlation between miR-375 expression and JAK2 protein level in gastric cancer. Thus, these data suggest that miR-375 may function as a tumor suppressor to regulate gastric cancer cell proliferation potentially by targeting the JAK2 oncogene, implicating a role of miR-375 in the pathogenesis of gastric cancer.展开更多
MicroRNAs （miRNAs） are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in b...MicroRNAs （miRNAs） are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB- 231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR- 205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A （VEGF-A） are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3＇-untranslated region （3＇-UTR） of ErbB3 and VEGF-A. Together, these results suggest that miR- 205 is a tumor suppressor in breast cancer.展开更多
MicroRNA-21(miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors.Through functional suppression,miR-21 is implicated in practically every walk of oncogenic life:t...MicroRNA-21(miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors.Through functional suppression,miR-21 is implicated in practically every walk of oncogenic life:the promotion of cell proliferation,invasion and metastasis,genome instability and mutation,inflammation,replicative immortalization,abnormal metabolism,angiogenesis,and evading apoptosis,immune destruction,and growth suppressors.In particular,miR-21 is strongly involved in apoptosis.In this article,we reviewed the experimentally validated targets of miR-21 and found that two thirds are linked to intrinsic and/or extrinsic pathways of cellular apoptosis.This suggests that miR-21 is an oncogene which plays a key role in resisting programmed cell death in cancer cells and that targeting apoptosis is a viable therapeutic option against cancers expressing miR-21.展开更多
AIM: To establish an accurate and rapid stem-loop reverse transcriptional real-time PCR (RT-PCR) method to quantify human let-7a miRNA in gastric cancer. METHODS: According to the sequence of let-7a miRNA,the stem-loo...AIM: To establish an accurate and rapid stem-loop reverse transcriptional real-time PCR (RT-PCR) method to quantify human let-7a miRNA in gastric cancer. METHODS: According to the sequence of let-7a miRNA,the stem-loop reverse transcriptional primer,the primers and quantitative MGB probes of real-time PCR were designed and synthesized. The dynamic range and the sensitivity of quantitative reverse transcriptional real-time PCR were determined. The levels of let-7a miRNA were examined in 32 gastric carcinoma samples by stem-loop RT-PCR method. RESULTS: The dynamic range and sensitivity of the let-7a miRNA quantification scheme were evaluated,the result showed the assay could precisely detect 10 copies of mature let-7a miRNA in as few as 0.05 ng of total RNA of gastric mucosa. The results of specificity analysis showed no fluorescence signal occurred even though 50 ng of human genomic DNA was added to the reverse transcription (RT) reaction. The expression level of let-7a miRNA in gastric tumor tissues was significantly lower compared to normal tissues in 14 samples from 32 patients. CONCLUSION: The stem-loop RT-PCR is a reliable method to detect let-7a miRNA which may play an important role in the development of gastric carcinoma.展开更多
Objective MicroRNAs （miRs） are attractive molecules to be considered as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer＇s disease （AD）. The goal of this study was to explore th...Objective MicroRNAs （miRs） are attractive molecules to be considered as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer＇s disease （AD）. The goal of this study was to explore their potential value as biomarkers for the diagnosis of AD.Methods The expression levels of exosomal miR-135a, -193b, and -384 in the serum from mild cognitive impairment （MCI）, dementia of Alzheimer-type （DAT）, Parkinson＇s disease with dementia （PDD）, and vascular dementia （VaD） patients were measured with a real-time quantitative reverse transcriptase PCR （qRT-PCR） method.Results Both serum exosome miR-135a and miR-384 were up-regulated while miR-193b was down-regulated in serum of AD patients compared with that of normal controls. Exosome miR-384 was the best among the three miRs to discriminate AD, VaD, and PDD. Using the cut-off value could better interpret these laboratory test results than reference intervals in the AD diagnosis. ROC curve showed that the combination of miR-135a, -193b, and -384 was proved to be better than a particular one for early AD diagnosis.Conclusion Our results indicated that the exosomal miRs in the serum were not only potential biomarker of AD early diagnosis, but might also provide novel insights into the screen and prevention of the disease.展开更多
MicroRNAs are short regulatory RNAs that negatively modulate gene expression at the post-transcriptional level, and are deeply involved in the pathogenesis of several types of cancers. To investigate whether specific ...MicroRNAs are short regulatory RNAs that negatively modulate gene expression at the post-transcriptional level, and are deeply involved in the pathogenesis of several types of cancers. To investigate whether specific miRNAs and their target genes participate in the molecular pathogenesis of laryngeal carcinoma, oligonucleotide microarrays were used to assess the differential expression profiles of microRNAs and mRNAs in laryngeal carcinoma tissues compared with normal tissues. The oncogeuic miRNA, microRNA-21 （miR-21）, was found to he npregulated in laryngeal carcinoma tissues. Knockdown of miR-21 by specific antisense oligonucleotides inhibited the proliferation potential of HEp-2 cells, whereas overexpression of miR-21 elevated growth activity of the cells, as detected by the colony formation assay. The cell number reduction caused by miR-21 inhibition was due to the loss of control of the G1-S phase transition, instead of a noticeable increase in apoptosis. Subsequently, a new target gene of miR- 21, BTG2, was found to be downregulated in laryngeal carcinoma tissues. BTG2 is known to act as a pan-cell cycle regulator and tumor suppressor. These findings indicate that aberrant expression of miR-21 may contribute to the malignant phenotype of laryngeal carcinoma by maintaining a low level of BTG2. The identification of the oneogenic miR-21 and its target gene, BTG2, in laryngeal carcinoma is potentially valuable for cancer diagnosis and therapy.展开更多
基金provided by the British Heart Foundation,UK(Grant No.CH/15/1/31199)
文摘Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA （lncRNA）, a heteroge- neous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA （miRNA） pathways, lncRNA has been shown to act as both a source and an inhi- bitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying com- plexes by directing them to specific loci.
文摘Seventy-five previously known plant microRNAs (miRNAs) were classified into 14 families according to their gene sequence identity. A total of 18,694 plant expressed sequence tags (EST) were found in the GenBank EST databases by comparing all previously known Arabidopsis miRNAs to GenBank’s plant EST databases with BLAST algorithms. After removing the EST sequences with high numbers (more than 2) of mismatched nucleotides, a total of 812 EST contigs were identified. After predicting and scoring the RNA secondary structure of the 812 EST sequences using mFold software, 338 new potential miRNAs were identified in 60 plant species. miRNAs are widespread. Some microRNAs may highly conserve in the plant kingdom, and they may have the same ancestor in very early evolution. There is no nucleotide substitution in most miRNAs among many plant species. Some of the new identified potential miRNAs may be induced and regulated by environmental biotic and abiotic stresses. Some may be preferentially expressed in specific tissues, and are regulated by developmental switching. These findings suggest that EST analysis is a good alternative strategy for identifying new miRNA candidates, their targets, and other genes. A large number of miRNAs exist in different plant species and play important roles in plant developmental switching and plant responses to environmental abiotic and biotic stresses as well as signal transduction. Environmental stresses and developmental switching may be the signals for synthesis and regulation of miRNAs in plants. A model for miRNA induction and expression, and gene regulation by miRNA is hypothesized.
文摘Gastric cancer is one of the leading causes of cancer mortality in the world. Aberrant expression of microRNAs (miRNAs) is the hallmark of this disease. MiRNAs are endogenous non-coding RNAs that are involved in many biological processes (e.g., cell proliferation, differentiation, apoptosis, invasion and development) through gene repression. Deregulation of miRNA expression in gastric tumors and cancer cell lines have been documented to contribute in tumorigenesis, and the expression signature may correlate with different cancer types and clinicopathological features. Here, we summarized the updated gastric cancer-associated miRNAs and the downstream targets in the process of tumorigenesis. Recently, many researchers make use of the miRNA microarray platform to profile miRNA expression in gastric cancer and correlated with different clinical parameters. Its application on cancer diagnosis, prognosis and predicting treatment response rate are still underway and needs further investigation. Emerging roles of miRNAs with oncogenic or tumor suppressive properties in gastric tumorigenesis were discussed. Epigenetic silencing of miRNA by hypermethylation of promoter CpG island was also observed in gastric cancer. However, detailed mechanisms of how miRNAs regulate gene expression in gastric cancer has not been well studied. In this review, we highlight the up-to-date findings on the deregulated miRNAs in gastric cancer, and the potential use of miRNA in the clinical settings, such as diagnostic/prognostic markers and chemotherapeutic tools.
基金supported by grants from the National Natural Science Foundation of China(No.30772549)the Medical Sci-Tech Development Foundation from Health Department of Jiangsu Province(No.P200965)
文摘Studies have shown cell-free microRNA(miRNA) circulating in the serum and plasma with specific expression in cancer,indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy.This study was to investigate whether plasma miRNA-21(miR-21) can be used as a biomarker for the early detection of non-small cell lung cancer(NSCLC) and to explore its association with clinicopathologic features and sensitivity to platinum-based chemotherapy.We used real-time RT-PCR to investigate the expression of miR-21 in the plasma of 63 NSCLC patients and 30 healthy controls and correlated the findings with early diagnosis,pathologic parameters,and treatment.Thirty-five patients(stages IIIB and IV) were evaluable for chemotherapeutic responses:11 had partial response(PR);24 had stable and progressive disease(SD+PD).Plasma miR-21 was significantly higher in NSCLC patients than in age-and sex-matched controls(P<0.001).miR-21 was related to TNM stage(P<0.001),but not related to age,sex,smoking status,histological classification,lymph node status,and metastasis(all P>0.05).This marker yielded a receiver operating characteristic(ROC) curve area of 0.775(95% CI:0.681-0.868) with 76.2% sensitivity and 70.0% specificity.Importantly,miR-21 plasma levels in PR samples were several folds lower than that in SD plus PD samples(P=0.049),and were close to that in healthy controls(P=0.130).Plasma miR-21 can serve as a circulating tumor biomarker for the early diagnosis of NSCLC and is related to the sensitivity to platinum-base chemotherapy.
基金supported by grants from the National Natural Science Foundation of China(81673760 and 81874397).
文摘Epithelial-to-mesenchymal transition(EMT)is implicated in a wide array of malignant behaviors of cancers,including proliferation,invasion,and metastasis.Most notably,previou studies have indicated that both cancer stem-like properties and drug resistance were associated with EMT.Furthermore,microRNAs(miRNAs)play a pivotal role in the regulation of EMT phenotype,as a result,some miRNAs impact cancer stemness and drug resistance.Therefore,understanding the relationship between EMT-associated miRNAs and cancer stemness/drug resistance is beneficial to both basic research and clinical treatment.In this review,we preliminarily looked into the various roles that the EMT-associated miRNAs play in the stem-like nature of malignant cells.Then,we reviewed the interaction between EMT-associated miRNAs and the drugresistant complex signaling pathways of multiple cancers including lung cancer,gastric cancer,gynecologic cancer,breast cancer,liver cancer,colorectal cancer,pancreatic cancer,esophageal cancer,and nasopharyngeal cancer.We finally discussed the relationship between EMT,cancer stemness,and drug resistance,as well as looked forward to the potential applications of miRNA therapy for malignant tumors.
文摘MicroRNAs(miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathological processes, such as development, cell differentiation, proliferation, apoptosis and tumor growth. miRNAs work as small guide molecules in RNA silencing, by negatively regulating the expression of several genes both at mRNA and protein level, by degrading their mRNA target and/or by silencing translation. One of the most recent advances in the field is the comprehension of their role in oncogenesis. The number of miRNA genes is increasing and an alteration in the level of miRNAs is involved in the initiation, progression and metastases formation of several tumors. Some tumor types show a distinct miRNA signature that distinguishes them from normal tissues and from other cancer types. Genetic and biochemical evidence supports the essential role of miRNAs in tumor development. Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the cause of this dysregulation is still unknown. Here, we discuss the biogenesis of miRNAs, focusing on the mechanisms by which they regulate protein synthesis. In addition we debate on their role in cancer, highlighting their potential to become therapeutic targets.
基金Supported by NIAAA Grants No. AA017729Supported by NIAAA Grants No. AA011576
文摘Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4 (TLR4) complex in LPS recognition and the importance of the TLR4-induced signaling pathways are evaluated in ALD.
基金Supplementary information is linked to the online version of the paper on Cell Research website.Acknowledgments This work was supported by the National Natural Scientific Foundation of China （30901714, 30671070 and 30771107）, the Ministry of Science and Technology of China （2007CB914500）, the Ministry of Education of China （NCET-06-0530）, the Ministry of Health of China （WKJ2006-2-014）, the Postdoctoral Science Foundation of China （20070421179）, the Department of Science and Technology of Zhejiang Province （2009F80032）, and the Natural Scientific Foundation of Zhejiang Province, China （R205291, Y206103 and 2007R10G2010103）.
文摘Emerging evidence has shown the association of aberrantly expressed microRNAs （miRNAs） with tumor development and progression. However, little is known about the potential role of miRNAs in gastric carcinogenesis. Here, we performed miRNA microarray to screen miRNAs differentially expressed in the paired gastric cancer and their adjacent nontumor tissues and found that miR-375 was greatly downregulated in gastric cancer tissues. Quantitative real-time PCR analysis verified that miR-375 expression was significantly decreased in more than 90% of primary gastric cancers compared with their nontumor counterparts from patients undergoing gastric resection. Overexpression of miR-375 significantly inhibited gastric cancer cell proliferation in vitro and in vivo. Forced expression of miR-375 in gastric cancer cells significantly reduced the protein level of Janus kinase 2 （JAK2） and repressed the activity of a luciferase reporter carrying the 3＇-untranslated region of JAK2, which was abolished by mutation of the predicted miR-375-binding site, indicating that JAK2 may be a miR-375 target gene. Either inhibition of JAK2 activity by AG490 or silencing of JAK2 by RNAi suppressed gastric cancer cell proliferation resembling that of miR-375 overexpression. Moreover, ectopic expression of JAK2 can partially reverse the inhibition of cell proliferation caused by miR-375. Finally, we found a significant inverse correlation between miR-375 expression and JAK2 protein level in gastric cancer. Thus, these data suggest that miR-375 may function as a tumor suppressor to regulate gastric cancer cell proliferation potentially by targeting the JAK2 oncogene, implicating a role of miR-375 in the pathogenesis of gastric cancer.
文摘MicroRNAs （miRNAs） are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB- 231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR- 205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A （VEGF-A） are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3＇-untranslated region （3＇-UTR） of ErbB3 and VEGF-A. Together, these results suggest that miR- 205 is a tumor suppressor in breast cancer.
基金supported by the Diabetes and Obesity Center funded by NCRR/NIH(P20RR024489)the Center for Environmental Genomics and Integrated Biology fundedby NIEHS/NIH(P30ES014443)+1 种基金the Scientist Development Grant from American Heart Association(0830288N)a R01 grant from National Institutes of Health(CA138688)
文摘MicroRNA-21(miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors.Through functional suppression,miR-21 is implicated in practically every walk of oncogenic life:the promotion of cell proliferation,invasion and metastasis,genome instability and mutation,inflammation,replicative immortalization,abnormal metabolism,angiogenesis,and evading apoptosis,immune destruction,and growth suppressors.In particular,miR-21 is strongly involved in apoptosis.In this article,we reviewed the experimentally validated targets of miR-21 and found that two thirds are linked to intrinsic and/or extrinsic pathways of cellular apoptosis.This suggests that miR-21 is an oncogene which plays a key role in resisting programmed cell death in cancer cells and that targeting apoptosis is a viable therapeutic option against cancers expressing miR-21.
文摘AIM: To establish an accurate and rapid stem-loop reverse transcriptional real-time PCR (RT-PCR) method to quantify human let-7a miRNA in gastric cancer. METHODS: According to the sequence of let-7a miRNA,the stem-loop reverse transcriptional primer,the primers and quantitative MGB probes of real-time PCR were designed and synthesized. The dynamic range and the sensitivity of quantitative reverse transcriptional real-time PCR were determined. The levels of let-7a miRNA were examined in 32 gastric carcinoma samples by stem-loop RT-PCR method. RESULTS: The dynamic range and sensitivity of the let-7a miRNA quantification scheme were evaluated,the result showed the assay could precisely detect 10 copies of mature let-7a miRNA in as few as 0.05 ng of total RNA of gastric mucosa. The results of specificity analysis showed no fluorescence signal occurred even though 50 ng of human genomic DNA was added to the reverse transcription (RT) reaction. The expression level of let-7a miRNA in gastric tumor tissues was significantly lower compared to normal tissues in 14 samples from 32 patients. CONCLUSION: The stem-loop RT-PCR is a reliable method to detect let-7a miRNA which may play an important role in the development of gastric carcinoma.
基金supported by the National Key Research and Development Program of China[2016YFC1306300]the National Natural Science Foundation of China[No.81401734]+1 种基金the National Research Foundation for the Doctoral Program of Higher Education of China[No.20121107110001]the National Natural Science Foundation of China[No.81472007]
文摘Objective MicroRNAs （miRs） are attractive molecules to be considered as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer＇s disease （AD）. The goal of this study was to explore their potential value as biomarkers for the diagnosis of AD.Methods The expression levels of exosomal miR-135a, -193b, and -384 in the serum from mild cognitive impairment （MCI）, dementia of Alzheimer-type （DAT）, Parkinson＇s disease with dementia （PDD）, and vascular dementia （VaD） patients were measured with a real-time quantitative reverse transcriptase PCR （qRT-PCR） method.Results Both serum exosome miR-135a and miR-384 were up-regulated while miR-193b was down-regulated in serum of AD patients compared with that of normal controls. Exosome miR-384 was the best among the three miRs to discriminate AD, VaD, and PDD. Using the cut-off value could better interpret these laboratory test results than reference intervals in the AD diagnosis. ROC curve showed that the combination of miR-135a, -193b, and -384 was proved to be better than a particular one for early AD diagnosis.Conclusion Our results indicated that the exosomal miRs in the serum were not only potential biomarker of AD early diagnosis, but might also provide novel insights into the screen and prevention of the disease.
基金Acknowledgments This work was supported by grants from the National Natural Science Foundation of China （No. 30873017） and the Key Program of the Natural Science Foundation of Tianjing （No. 08JCZDJC23300）. We thank Tianjin First Center Hospital for providing human laryngeal tissue samples. We also thank the College of Public Health of Tianjin Medical University for the technical assistance in fluorescent detection. The ArrayExpress accession numbers of miRNA microarray design and cDNA microarray design are A-MEXP-1506 and A-MEXP-1511. The ArrayExpress accession numbers of miRNA microarray experiment and eDNA microarray experiment are E-MEXP-2039 and E-MEXP-2056.
文摘MicroRNAs are short regulatory RNAs that negatively modulate gene expression at the post-transcriptional level, and are deeply involved in the pathogenesis of several types of cancers. To investigate whether specific miRNAs and their target genes participate in the molecular pathogenesis of laryngeal carcinoma, oligonucleotide microarrays were used to assess the differential expression profiles of microRNAs and mRNAs in laryngeal carcinoma tissues compared with normal tissues. The oncogeuic miRNA, microRNA-21 （miR-21）, was found to he npregulated in laryngeal carcinoma tissues. Knockdown of miR-21 by specific antisense oligonucleotides inhibited the proliferation potential of HEp-2 cells, whereas overexpression of miR-21 elevated growth activity of the cells, as detected by the colony formation assay. The cell number reduction caused by miR-21 inhibition was due to the loss of control of the G1-S phase transition, instead of a noticeable increase in apoptosis. Subsequently, a new target gene of miR- 21, BTG2, was found to be downregulated in laryngeal carcinoma tissues. BTG2 is known to act as a pan-cell cycle regulator and tumor suppressor. These findings indicate that aberrant expression of miR-21 may contribute to the malignant phenotype of laryngeal carcinoma by maintaining a low level of BTG2. The identification of the oneogenic miR-21 and its target gene, BTG2, in laryngeal carcinoma is potentially valuable for cancer diagnosis and therapy.
