Over the past decade, research has shown that aberrant expression of micro RNA(mi RNA) is involved in colorectal cancer development and progression. Micro RNAs are small sequences of non-coding RNA that regulate expre...Over the past decade, research has shown that aberrant expression of micro RNA(mi RNA) is involved in colorectal cancer development and progression. Micro RNAs are small sequences of non-coding RNA that regulate expression of genes involved in important cellular functions, such as cell differentiation, multiplication, and apoptosis. A specific mi RNA may display the effects of a tumor suppressor or oncogene. Altered mi RNA expression is found in colorectal cancer(CRC) and patterns of mi RNA expression correlate with CRC detection and outcome. Studies also have examined the use of circulating serum mi RNA and fecal mi RNA expression as non-invasive markers for early detection. Here, we review recent evidence demonstrating the potential role of mi RNA in CRC and the implications of its use in the diagnosis, prognosis, and management of CRC.展开更多
Gastric cancer(GC) is the third most common cause of cancer-related death in the world,representing a major global health issue. Although the incidence of GC is declining,the outcomes for GC patients remain dismal bec...Gastric cancer(GC) is the third most common cause of cancer-related death in the world,representing a major global health issue. Although the incidence of GC is declining,the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC,including serum carcinoembryonic antigen and carbohydrate antigen 19-9,are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules,including oncogenes,tumor suppressor genes,micro RNAs and long non-coding RNAs,and DNA methylation,as novel molecular markers,although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review,the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized,and certain highlighted papers are examined.展开更多
AIM To assess disease-specific circulating micro RNAs(mi RNAs) in non-alcoholic steatohepatitis(NASH) patients.METHODS A total of 111 biopsy-proven non-alcoholic fatty liver disease(NAFLD) or chronic hepatitis B(CHB) ...AIM To assess disease-specific circulating micro RNAs(mi RNAs) in non-alcoholic steatohepatitis(NASH) patients.METHODS A total of 111 biopsy-proven non-alcoholic fatty liver disease(NAFLD) or chronic hepatitis B(CHB) patients and healthy controls from China's Mainland were enrolled to measure their serum levels of mi R-122,-125 b,-146 b,-16,-21,-192,-27 b and-34 a. The correlations between serum mi RNAs and histological features of NAFLD were determined. The diagnostic value of mi RNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18(CK-18), fibrosis-4(FIB-4), and aspartate aminotransferase to platelet ratio index(APRI), respectively.RESULTS Circulating mi R-122,-16,-192 and-34 a showed differential expression levels between NAFLD and CHB patients, and mi R-34 a had an approximately 2-fold increase in NAFLD samples compared with that of CHB samples(P < 0.01). Serum mi R-122,-192 and-34a levels were correlated with steatosis(R = 0.302, 0.323 and 0.470, respectively, P < 0.05) and inflammatory activity(R = 0.445, 0.447 and 0.517, respectively, P < 0.01); only serum mi R-16 levels were associated with fibrosis(R = 0.350, P < 0.05) in patients with NAFLD. The diagnostic value of mi R-34 a for NASH(area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but mi R-16 showed a limited performance in the diagnosis of significant fibrosis in NASH.CONCLUSION Circulating mi R-34 a may serve as a disease-specific noninvasive biomarker for the diagnosis of NASH.展开更多
Cancer-associated fibroblasts(CAFs) are important components of various types of tumors,including gastric cancer(GC).During tumorigenesis and progression,CAFs play critical roles in tumor invasion and metastasis via a...Cancer-associated fibroblasts(CAFs) are important components of various types of tumors,including gastric cancer(GC).During tumorigenesis and progression,CAFs play critical roles in tumor invasion and metastasis via a series of functions including extracellular matrix deposition,angiogenesis,metabolism reprogramming and chemoresistance.However,the mechanism of the interaction between gastric cancer cells and CAFs remains largely unknown.Micro RNAs(mi RNAs) are a class of non-coding small RNA molecules,and their expression in CAFs not only regulates the expression of a number of target genes but also plays an essential role in the communication between tumor cells and CAFs.In this review,we provide an overview of recent studies on CAF mi RNAs in GC and the relevant signaling pathways in gastrointestinal tumors.Focusing the attention on these signaling pathways may help us better understand their role in tumor invasion and metastasis and identify new molecular targets for therapeutic strategies.展开更多
Biomarkers for surveillance, diagnosis and prediction of prognosis in patients with hepatocellular carcinoma(HCC) are currently not ready for introduction into clinical practice because of limited sensitivity and spec...Biomarkers for surveillance, diagnosis and prediction of prognosis in patients with hepatocellular carcinoma(HCC) are currently not ready for introduction into clinical practice because of limited sensitivity and specificity. Especially for the early detection of small HCC novel biomarkers are needed to improve the current effectiveness of screening performed byultrasound. The use of high-throughput technologies in hepatocellular research allows to identify molecules involved in the complex pathways in hepatocarcinogenesis. Several invasive and non-invasive biomarkers have been identified already and have been evaluated in different clinical settings. Gene signatures with prognostic potential have been identified by gene expression profiling from tumor tissue. However, a single "all-in-one" biomarker that fits all-surveillance, diagnosis, prediction of prognosis-has not been found so far. The future of biomarkers most probably lies in a combination of non-invasive biomarkers, imaging and clinical parameters in a surveillance setting. Molecular profiling of tumorous and non-tumorous liver tissue may allow a prediction of prognosis for the individual patient and hopefully clear the way for individual treatment approaches. This article gives an overview on current developments in biomarker research in HCC with a focus on currently available and novel biomarkers, in particular on micro RNA.展开更多
Chronic infection with the hepatitis B virus(HBV) is the leading risk factor for the development of hepatocellular carcinoma(HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause...Chronic infection with the hepatitis B virus(HBV) is the leading risk factor for the development of hepatocellular carcinoma(HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause of cancer-related death in the world. Unfortunately, the molecular mechanisms that contribute to the development of HBV-associated HCC remain incompletely understood. Recently, micro RNAs(mi RNAs), a family of small non-coding RNAs that play a role primarily in post-transcriptional gene regulation, have been recognized as important regulators of cellular homeostasis, and altered regulation of mi RNA expression has been suggested to play a significant role in virus-associated diseases and the development of many cancers. With this in mind, many groups have begun to investigate the relationship between mi RNAs and HBV replication and HBV-associated disease. Multiple findings suggest that some mi RNAs, such as mi R-122, and mi R-125 and mi R-199 family members, are playing a role in HBV replication and HBV-associated disease, including the development of HBV-associated HCC. In this review, we discuss the current state of our understanding of the relationship between HBV and mi RNAs, including how HBV affects cellular mi RNAs, how these mi RNAs impact HBV replication, and the relationship between HBV-mediated mi RNA regulation and HCC development. We also address the impact of challenges in studying HBV, such as the lack of an effective model system for infectivity and a reliance on transformed cell lines, on our understanding of the relationship between HBV and mi RNAs, and proposepotential applications of mi RNA-related techniques that could enhance our understanding of the role mi RNAs play in HBV replication and HBV-associated disease, ultimately leading to new therapeutic options and improved patient outcomes.展开更多
AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gas...AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gastric cancer-associated fibroblast(GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside Ⅳ. Conditioned media were prepared from GNFs,GCAFs,control-treated GCAFs,and astragaloside Ⅳ-treated GCAFs,and used to culture BGC-823 human gastric cancer cells. Proliferation,migration and invasion capacities of BGC-823 cells were determined by MTT,wound healing,and Transwell invasion assays,respectively. The action mechanism of astragaloside Ⅳ was investigated by detecting the expression of micro RNAs and the expression and secretion of the oncogenic factor,macrophage colonystimulating factor(M-CSF),and the tumor suppressive factor,tissue inhibitor of metalloproteinase 2(TIMP2),in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined.RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation,migration,and invasion than GNFs(P < 0.01). Astragaloside Ⅳ treatment strongly inhibited the proliferation-,migration-and invasion-promoting capacities of GCAFs(P < 0.05 for 10 μmol/L,P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs,GCAFs expressed a lower level of micro RNA-214(P < 0.01) and a higher level of micro RNA-301 a(P < 0.01). Astragaloside Ⅳ treatment significantly upregulated micro RNA-214 expression(P < 0.01) and down-regulated micro RNA-301 a expression(P < 0.01) in GCAFs. Reestablishing the micro RNA expression balance subsequently suppressed M-CSF production(P < 0.01) and secretion(P < 0.05),and elevated TIMP2 production(P < 0.01) and secretion(P < 0.05). Consequently,the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astraga展开更多
AIM:To investigate the biological role of mi R-1290 in esophageal squamous cell carcinoma(ESCC) progression and invasion and the underlying mechanism.METHODS:Quantitative real-time polymerase chain reaction(q RT-PCR) ...AIM:To investigate the biological role of mi R-1290 in esophageal squamous cell carcinoma(ESCC) progression and invasion and the underlying mechanism.METHODS:Quantitative real-time polymerase chain reaction(q RT-PCR) was performed to evaluate mi R-1290 expression in ESCC tissue samples.The roles of mi R-1290 in cell proliferation,migration and invasion were identified using mi R-1290 mimic-transfected cells.In addition,the regulatory effect of mi R-1290 on suppressor of cancer cell invasion(SCAI) was evaluated using q RT-PCR,Western blot analysis and a dual luciferase reporter assay.RESULTS:mi R-1290 was significantly upregulated in ESCC tissue samples compared with normal adjacent tissues(9.213 ± 1.150 vs 1.000 ± 0.0),(P < 0.01).Upregulation of mi R-1290 was associated with tumor differentiation(P = 0.021),N classification(P = 0.006) and tumor-node-metastasis stage(P = 0.021) in ESCC patients.Moreover,ectopic mi R-1290 expression potently promoted ESCC cell growth(P < 0.01),migration(P < 0.01) and invasion(P < 0.01) in vitro.mi R-1290 overexpression in ESCC cell lines decreased SCAI expression at the translational level and reduced SCAI-driven luciferase-reporter activity(P < 0.01).CONCLUSION:Our findings suggested that mi R-1290 may play an oncogenic role in cellular processes of ESCC.展开更多
Gallbladder cancer(GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment op...Gallbladder cancer(GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. Micro RNAs(mi RNAs) are small, noncoding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or oncogenes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since mi RNA signature is tissue specific, here, we focused on current data concerning the mi RNAs abberations in GBC pathogenesis. In GBC, mi RNAs with tumor suppressor activity(mi R-135-5p, mi R-335, mi R-34 a, mi R-26 a, mi R-146b-5p, Mir-218-5p, mi R-1, mi R-145, mir-130a) were found downregulated, while those with oncogenic property(mi R-20 a, mi R-182, mir-155) were upregulated. The expression profile of mi RNAs was significantly associated with GBC prognosis and prediction, and forced over-expression/ inhibition of these mi RNAs was shown to affect tumor growth and development. Further, differential expression of mi RNAs in the blood samples of GBC patients suggest mi RNAs as promising noninvasive biomarker. Thus, mi RNAs represent potential candidate for GBC management, though many hurdles need to be overcome before mi RNAs therapy can be clinically applied to GBC prevention and treatment.展开更多
Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent...Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent posttranscriptional suppression of transgene expression has been emerging as powerful new technology to increase the specificity of vector-mediated transgene expression. Micro RNAs are small non-coding RNAs and often expressed in a tissue-, lineage-, activation- or differentiation-specific pattern. They typically regulate gene expression by binding to imperfectly complementary sequences in the 3' untranslated region(UTR) of the m RNA. To control exogenous transgene expression, tandem repeats of artificial micro RNA target sites are usually incorporated into the 3' UTR of the transgene expression cassette, leading to subsequent degradation of transgene m RNA in cel s expressing the corresponding micro RNA. This targeting strategy, first shown for lentiviral vectors in antigen presenting cells, has now been used for tissue-specific expression of vector-encoded therapeutic transgenes, to reduce immune response against the transgene, to control virus tropism for oncolytic virotherapy, to increase safety of live attenuated virus vaccines and to identify and select cell subsets for pluripotent stem cell therapies, respectively. This review provides an introduction into the technical mechanism underlying micro RNA-regulation, highlights new developments in this field and gives an overview of applications of micro RNA-regulated viral vectors for cardiac, suicide gene cancer and hematopoietic stem cell therapy, as well as for treatment of neurological and eye diseases.展开更多
文摘Over the past decade, research has shown that aberrant expression of micro RNA(mi RNA) is involved in colorectal cancer development and progression. Micro RNAs are small sequences of non-coding RNA that regulate expression of genes involved in important cellular functions, such as cell differentiation, multiplication, and apoptosis. A specific mi RNA may display the effects of a tumor suppressor or oncogene. Altered mi RNA expression is found in colorectal cancer(CRC) and patterns of mi RNA expression correlate with CRC detection and outcome. Studies also have examined the use of circulating serum mi RNA and fecal mi RNA expression as non-invasive markers for early detection. Here, we review recent evidence demonstrating the potential role of mi RNA in CRC and the implications of its use in the diagnosis, prognosis, and management of CRC.
文摘Gastric cancer(GC) is the third most common cause of cancer-related death in the world,representing a major global health issue. Although the incidence of GC is declining,the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC,including serum carcinoembryonic antigen and carbohydrate antigen 19-9,are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules,including oncogenes,tumor suppressor genes,micro RNAs and long non-coding RNAs,and DNA methylation,as novel molecular markers,although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review,the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized,and certain highlighted papers are examined.
基金Supported by grants from the State Key Development Program for Basic Research of China,No.2012CB517501National Natural Science Foundation of China,No.81270491 and No.81470840+1 种基金Hundred Talents Program of the Shanghai Board of Health,No.XBR2011007Program of the Shanghai Committee of Science and Technology,No.10411956300
文摘AIM To assess disease-specific circulating micro RNAs(mi RNAs) in non-alcoholic steatohepatitis(NASH) patients.METHODS A total of 111 biopsy-proven non-alcoholic fatty liver disease(NAFLD) or chronic hepatitis B(CHB) patients and healthy controls from China's Mainland were enrolled to measure their serum levels of mi R-122,-125 b,-146 b,-16,-21,-192,-27 b and-34 a. The correlations between serum mi RNAs and histological features of NAFLD were determined. The diagnostic value of mi RNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18(CK-18), fibrosis-4(FIB-4), and aspartate aminotransferase to platelet ratio index(APRI), respectively.RESULTS Circulating mi R-122,-16,-192 and-34 a showed differential expression levels between NAFLD and CHB patients, and mi R-34 a had an approximately 2-fold increase in NAFLD samples compared with that of CHB samples(P < 0.01). Serum mi R-122,-192 and-34a levels were correlated with steatosis(R = 0.302, 0.323 and 0.470, respectively, P < 0.05) and inflammatory activity(R = 0.445, 0.447 and 0.517, respectively, P < 0.01); only serum mi R-16 levels were associated with fibrosis(R = 0.350, P < 0.05) in patients with NAFLD. The diagnostic value of mi R-34 a for NASH(area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but mi R-16 showed a limited performance in the diagnosis of significant fibrosis in NASH.CONCLUSION Circulating mi R-34 a may serve as a disease-specific noninvasive biomarker for the diagnosis of NASH.
文摘Cancer-associated fibroblasts(CAFs) are important components of various types of tumors,including gastric cancer(GC).During tumorigenesis and progression,CAFs play critical roles in tumor invasion and metastasis via a series of functions including extracellular matrix deposition,angiogenesis,metabolism reprogramming and chemoresistance.However,the mechanism of the interaction between gastric cancer cells and CAFs remains largely unknown.Micro RNAs(mi RNAs) are a class of non-coding small RNA molecules,and their expression in CAFs not only regulates the expression of a number of target genes but also plays an essential role in the communication between tumor cells and CAFs.In this review,we provide an overview of recent studies on CAF mi RNAs in GC and the relevant signaling pathways in gastrointestinal tumors.Focusing the attention on these signaling pathways may help us better understand their role in tumor invasion and metastasis and identify new molecular targets for therapeutic strategies.
文摘Biomarkers for surveillance, diagnosis and prediction of prognosis in patients with hepatocellular carcinoma(HCC) are currently not ready for introduction into clinical practice because of limited sensitivity and specificity. Especially for the early detection of small HCC novel biomarkers are needed to improve the current effectiveness of screening performed byultrasound. The use of high-throughput technologies in hepatocellular research allows to identify molecules involved in the complex pathways in hepatocarcinogenesis. Several invasive and non-invasive biomarkers have been identified already and have been evaluated in different clinical settings. Gene signatures with prognostic potential have been identified by gene expression profiling from tumor tissue. However, a single "all-in-one" biomarker that fits all-surveillance, diagnosis, prediction of prognosis-has not been found so far. The future of biomarkers most probably lies in a combination of non-invasive biomarkers, imaging and clinical parameters in a surveillance setting. Molecular profiling of tumorous and non-tumorous liver tissue may allow a prediction of prognosis for the individual patient and hopefully clear the way for individual treatment approaches. This article gives an overview on current developments in biomarker research in HCC with a focus on currently available and novel biomarkers, in particular on micro RNA.
基金Supported by Pennsylvania state CURE grant,No.4100057658,[to Steel LF and Bouchard MJ(partially)]a Ruth L Kirschstein(F31)Predoctoral Fellowship,No.5F31CA171712-03,[to Lamontagne J(partially)]
文摘Chronic infection with the hepatitis B virus(HBV) is the leading risk factor for the development of hepatocellular carcinoma(HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause of cancer-related death in the world. Unfortunately, the molecular mechanisms that contribute to the development of HBV-associated HCC remain incompletely understood. Recently, micro RNAs(mi RNAs), a family of small non-coding RNAs that play a role primarily in post-transcriptional gene regulation, have been recognized as important regulators of cellular homeostasis, and altered regulation of mi RNA expression has been suggested to play a significant role in virus-associated diseases and the development of many cancers. With this in mind, many groups have begun to investigate the relationship between mi RNAs and HBV replication and HBV-associated disease. Multiple findings suggest that some mi RNAs, such as mi R-122, and mi R-125 and mi R-199 family members, are playing a role in HBV replication and HBV-associated disease, including the development of HBV-associated HCC. In this review, we discuss the current state of our understanding of the relationship between HBV and mi RNAs, including how HBV affects cellular mi RNAs, how these mi RNAs impact HBV replication, and the relationship between HBV-mediated mi RNA regulation and HCC development. We also address the impact of challenges in studying HBV, such as the lack of an effective model system for infectivity and a reliance on transformed cell lines, on our understanding of the relationship between HBV and mi RNAs, and proposepotential applications of mi RNA-related techniques that could enhance our understanding of the role mi RNAs play in HBV replication and HBV-associated disease, ultimately leading to new therapeutic options and improved patient outcomes.
基金Supported by the National Natural Science Foundation of China,No.81760552the Program of the Inner Mongolia Natural Science Foundation,No.2016MS0824 and No.2015MS0896+1 种基金the Program of“Keji Baiwan Gongcheng”of Inner Mongolia Medical University,No.YKD2015KJBW008the Supporting Program for Outstanding Youth in Science and Technology of Inner Mongolia Autonomous Region,No.NJYT-17-B30
文摘AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts,and to explore the underlying mechanism.METHODS Paired gastric normal fibroblast(GNF) and gastric cancer-associated fibroblast(GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside Ⅳ. Conditioned media were prepared from GNFs,GCAFs,control-treated GCAFs,and astragaloside Ⅳ-treated GCAFs,and used to culture BGC-823 human gastric cancer cells. Proliferation,migration and invasion capacities of BGC-823 cells were determined by MTT,wound healing,and Transwell invasion assays,respectively. The action mechanism of astragaloside Ⅳ was investigated by detecting the expression of micro RNAs and the expression and secretion of the oncogenic factor,macrophage colonystimulating factor(M-CSF),and the tumor suppressive factor,tissue inhibitor of metalloproteinase 2(TIMP2),in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined.RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation,migration,and invasion than GNFs(P < 0.01). Astragaloside Ⅳ treatment strongly inhibited the proliferation-,migration-and invasion-promoting capacities of GCAFs(P < 0.05 for 10 μmol/L,P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs,GCAFs expressed a lower level of micro RNA-214(P < 0.01) and a higher level of micro RNA-301 a(P < 0.01). Astragaloside Ⅳ treatment significantly upregulated micro RNA-214 expression(P < 0.01) and down-regulated micro RNA-301 a expression(P < 0.01) in GCAFs. Reestablishing the micro RNA expression balance subsequently suppressed M-CSF production(P < 0.01) and secretion(P < 0.05),and elevated TIMP2 production(P < 0.01) and secretion(P < 0.05). Consequently,the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astraga
基金Supported by grants from Innovative Team Project of Jiangsu Province,China,No.CXZZ11_0705
文摘AIM:To investigate the biological role of mi R-1290 in esophageal squamous cell carcinoma(ESCC) progression and invasion and the underlying mechanism.METHODS:Quantitative real-time polymerase chain reaction(q RT-PCR) was performed to evaluate mi R-1290 expression in ESCC tissue samples.The roles of mi R-1290 in cell proliferation,migration and invasion were identified using mi R-1290 mimic-transfected cells.In addition,the regulatory effect of mi R-1290 on suppressor of cancer cell invasion(SCAI) was evaluated using q RT-PCR,Western blot analysis and a dual luciferase reporter assay.RESULTS:mi R-1290 was significantly upregulated in ESCC tissue samples compared with normal adjacent tissues(9.213 ± 1.150 vs 1.000 ± 0.0),(P < 0.01).Upregulation of mi R-1290 was associated with tumor differentiation(P = 0.021),N classification(P = 0.006) and tumor-node-metastasis stage(P = 0.021) in ESCC patients.Moreover,ectopic mi R-1290 expression potently promoted ESCC cell growth(P < 0.01),migration(P < 0.01) and invasion(P < 0.01) in vitro.mi R-1290 overexpression in ESCC cell lines decreased SCAI expression at the translational level and reduced SCAI-driven luciferase-reporter activity(P < 0.01).CONCLUSION:Our findings suggested that mi R-1290 may play an oncogenic role in cellular processes of ESCC.
文摘Gallbladder cancer(GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. Micro RNAs(mi RNAs) are small, noncoding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or oncogenes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since mi RNA signature is tissue specific, here, we focused on current data concerning the mi RNAs abberations in GBC pathogenesis. In GBC, mi RNAs with tumor suppressor activity(mi R-135-5p, mi R-335, mi R-34 a, mi R-26 a, mi R-146b-5p, Mir-218-5p, mi R-1, mi R-145, mir-130a) were found downregulated, while those with oncogenic property(mi R-20 a, mi R-182, mir-155) were upregulated. The expression profile of mi RNAs was significantly associated with GBC prognosis and prediction, and forced over-expression/ inhibition of these mi RNAs was shown to affect tumor growth and development. Further, differential expression of mi RNAs in the blood samples of GBC patients suggest mi RNAs as promising noninvasive biomarker. Thus, mi RNAs represent potential candidate for GBC management, though many hurdles need to be overcome before mi RNAs therapy can be clinically applied to GBC prevention and treatment.
基金Supported by The Deutsche Forschungsgemeinschaft,Nos.FE785/2-2 and FE785/4-1the Bundesministerium für Bildung und Entwicklung,No.031A331
文摘Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent posttranscriptional suppression of transgene expression has been emerging as powerful new technology to increase the specificity of vector-mediated transgene expression. Micro RNAs are small non-coding RNAs and often expressed in a tissue-, lineage-, activation- or differentiation-specific pattern. They typically regulate gene expression by binding to imperfectly complementary sequences in the 3' untranslated region(UTR) of the m RNA. To control exogenous transgene expression, tandem repeats of artificial micro RNA target sites are usually incorporated into the 3' UTR of the transgene expression cassette, leading to subsequent degradation of transgene m RNA in cel s expressing the corresponding micro RNA. This targeting strategy, first shown for lentiviral vectors in antigen presenting cells, has now been used for tissue-specific expression of vector-encoded therapeutic transgenes, to reduce immune response against the transgene, to control virus tropism for oncolytic virotherapy, to increase safety of live attenuated virus vaccines and to identify and select cell subsets for pluripotent stem cell therapies, respectively. This review provides an introduction into the technical mechanism underlying micro RNA-regulation, highlights new developments in this field and gives an overview of applications of micro RNA-regulated viral vectors for cardiac, suicide gene cancer and hematopoietic stem cell therapy, as well as for treatment of neurological and eye diseases.
