目的:探究微小RNA(miR)-574-3p、序列相似家族3成员C(family with sequence similarity 3 member C,FAM3C)在食管癌组织中的表达,并分析二者与患者临床病理特征的关系。方法:选取2018年5月至2020年5月于本院行手术治疗的90例食管癌患者...目的:探究微小RNA(miR)-574-3p、序列相似家族3成员C(family with sequence similarity 3 member C,FAM3C)在食管癌组织中的表达,并分析二者与患者临床病理特征的关系。方法:选取2018年5月至2020年5月于本院行手术治疗的90例食管癌患者,收集术中留取的癌组织和癌旁组织标本。使用qRT-PCR法检测组织中miR-574-3p、FAM3C mRNA相对表达量;使用免疫组织化学法检测组织中FAM3C蛋白表达情况;采用Spearman等级相关分析食管癌组织中miR-574-3p、FAM3C的相关性;Kaplan-Meier法分析miR-574-3p、FAM3C与预后的关系。结果:食管癌患者癌组织中miR-574-3p低表达,FAM3C mRNA、FAM3C蛋白高表达(P<0.05)。食管癌组织中miR-574-3p、FAM3C蛋白表达水平具有负相关性(r=-0.420,P<0.05)。Pearson相关性分析显示,食管癌组织中miR-574-3p、FAM3C mRNA表达具有负相关性(r=-0.731,P<0.05)。miR-574-3p、FAM3C蛋白均与TNM分期、浸润程度、淋巴结转移有关(P<0.05)。miR-574-3p高表达组3年累积生存率为83.72%,显著高于miR-574-3p低表达组(53.19%);FAM3C高表达组3年累积生存率为56.86%,显著低于FAM3C低表达组(82.05%),差异均有统计学意义(log rankχ^(2)=10.175、7.290,P<0.05)。结论:食管癌组织中miR-574-3p表达水平较低,FAM3C表达水平较高,且二者具有负相关性,与临床病理特征中的TNM分期、浸润程度、淋巴结转移以及患者3年累积生存率有关。展开更多
目的:探讨microRNA-29c对人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2)生物学特性的影响。方法:培养1种人正常胰腺上皮细胞(HPDE)及4种人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2),采用real-time PCR法观察5种细胞系...目的:探讨microRNA-29c对人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2)生物学特性的影响。方法:培养1种人正常胰腺上皮细胞(HPDE)及4种人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2),采用real-time PCR法观察5种细胞系中microRNA-29c的表达差异,以microRNA-29c过表达腺病毒感染的PANC-1和MIA Pa Ca2细胞作为实验组,以空载体感染的PANC-1和MIA Pa Ca2细胞作为阴性对照组,采用细胞划痕实验、Transwell法检测两组细胞体外侵袭能力,Western blot检测两组细胞上皮间充质转化(EMT)相关蛋白波形蛋白(Vimentin)及E-钙粘蛋白(E-cadherin)的表达。结果:real-time-PCR显示各胰腺癌细胞系中microRNA-29c水平明显低于正常胰腺细胞系(P<0.05),细胞划痕实验发现感染腺病毒48 h后实验组PANC-1、MIA Pa Ca-2细胞的迁移距离明显短于阴性对照组(P<0.05),Transwell小室细胞侵袭实验发现实验组PANC-1和MIA Pa Ca-2细胞侵袭数量明显低于阴性对照组(P<0.05);Western blot蛋白免疫印迹结果显示PANC-1和MIA Pa Ca-2细胞过表达microRNA-29c后,Vimentin表达减少,E-cadherin表达增加。结论:microRNA-29c的过表达可有效抑制胰腺癌细胞的体外侵袭与转移,可能与Vimentin表达减少,E-cadherin表达增加有关,有望成为胰腺癌生物治疗的潜在靶点。展开更多
Micro RNAs(mi RNAs) are small noncoding RNAs. More than 2500 mature mi RNAs are detected in plants, animals and several types of viruses. Hepatitis C virus(HCV), which is a positive-sense, singlestranded RNA virus, do...Micro RNAs(mi RNAs) are small noncoding RNAs. More than 2500 mature mi RNAs are detected in plants, animals and several types of viruses. Hepatitis C virus(HCV), which is a positive-sense, singlestranded RNA virus, does not encode viral mi RNA. However, HCV infection alters the expression of host mi RNAs, either in cell culture or in patients with liver disease progression, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. In turn, host mi RNAs regulate HCV life cycle through directly binding to HCV RNAs or indirectly targeting cellular m RNAs. Increasing evidence demonstrates that mi RNAs are one of the centered factors in the interaction network between virus and host. The competitive viral and host RNA hypothesis proposes a latent cross-regulation pattern between host m RNAs and HCV RNAs. High loads of HCV RNA sequester and de-repress host mi RNAs from their normal host targets and thus disturb host gene expression, indicating a means of adaptation for HCV to establish a persistent infection. Some special mi RNAs are closely correlated with liver-specific disease progression and the changed levels of mi RNAs are even higher sensitivity and specificity than those of traditional proteins. Therefore, some of them can serve as novel diagnostic/prognostic biomarkers in HCVinfected patients with liver diseases. They are also attractive therapeutic targets for development of new anti-HCV agents.展开更多
Not only is chronic hepatitis C virus(HCV) infection a major public health problem,but also it can cause hepatocellular carcinoma and,more rarely,nonHodgkin's lymphoma.These characteristics mean that HCV is the on...Not only is chronic hepatitis C virus(HCV) infection a major public health problem,but also it can cause hepatocellular carcinoma and,more rarely,nonHodgkin's lymphoma.These characteristics mean that HCV is the only virus infecting humans that is able to cause two different cancers.The fine pathogenetic and molecular mechanisms by which HCV induces these two malignancies are not completely clear.In the last decade,it has been shown that microRNAs(miRNAs),a class of 21-23-nucleotide molecules modulating posttranscriptional gene expression,make an important contribution to the pathogenesis of several cancers and are also considered highly promising biomarkers.Here,we briefly describe the current knowledge about microRNAs' involvement in HCV-related molecular oncogenesis.We decided to focus our attention on studies fully conducted on ex vivo samples with this specific etiology,and on cultured cell lines partially or completely expressing the HCV genome.Some of the results reported in this review are controversial,possibly because of methodological issues,differences in sampling size and features,and ethnicity of patients.What is certain is that miRNAs play a remarkable role in regulating gene expression during oncogenetic processes and in viral infection.A clear understanding of their effects is fundamental to elucidating the mechanisms underlying virus-induced malignancies.展开更多
BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important r...BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10^(-3) mm^2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^(-3) mm^2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^(-3) mm^2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.展开更多
文摘目的:探讨microRNA-29c对人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2)生物学特性的影响。方法:培养1种人正常胰腺上皮细胞(HPDE)及4种人胰腺癌细胞(As PC-1、Bx PC-3、PANC-1、MIA Pa Ca-2),采用real-time PCR法观察5种细胞系中microRNA-29c的表达差异,以microRNA-29c过表达腺病毒感染的PANC-1和MIA Pa Ca2细胞作为实验组,以空载体感染的PANC-1和MIA Pa Ca2细胞作为阴性对照组,采用细胞划痕实验、Transwell法检测两组细胞体外侵袭能力,Western blot检测两组细胞上皮间充质转化(EMT)相关蛋白波形蛋白(Vimentin)及E-钙粘蛋白(E-cadherin)的表达。结果:real-time-PCR显示各胰腺癌细胞系中microRNA-29c水平明显低于正常胰腺细胞系(P<0.05),细胞划痕实验发现感染腺病毒48 h后实验组PANC-1、MIA Pa Ca-2细胞的迁移距离明显短于阴性对照组(P<0.05),Transwell小室细胞侵袭实验发现实验组PANC-1和MIA Pa Ca-2细胞侵袭数量明显低于阴性对照组(P<0.05);Western blot蛋白免疫印迹结果显示PANC-1和MIA Pa Ca-2细胞过表达microRNA-29c后,Vimentin表达减少,E-cadherin表达增加。结论:microRNA-29c的过表达可有效抑制胰腺癌细胞的体外侵袭与转移,可能与Vimentin表达减少,E-cadherin表达增加有关,有望成为胰腺癌生物治疗的潜在靶点。
基金Supported by National Natural Science Foundation of China No.81321004 and No.81322050National Mega-Project for“R&D for Innovative Drugs”+3 种基金Ministry of Science and TechnologyChina No.2012ZX09301-002-001Ministry of EducationChina No.NCET-12-0072
文摘Micro RNAs(mi RNAs) are small noncoding RNAs. More than 2500 mature mi RNAs are detected in plants, animals and several types of viruses. Hepatitis C virus(HCV), which is a positive-sense, singlestranded RNA virus, does not encode viral mi RNA. However, HCV infection alters the expression of host mi RNAs, either in cell culture or in patients with liver disease progression, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. In turn, host mi RNAs regulate HCV life cycle through directly binding to HCV RNAs or indirectly targeting cellular m RNAs. Increasing evidence demonstrates that mi RNAs are one of the centered factors in the interaction network between virus and host. The competitive viral and host RNA hypothesis proposes a latent cross-regulation pattern between host m RNAs and HCV RNAs. High loads of HCV RNA sequester and de-repress host mi RNAs from their normal host targets and thus disturb host gene expression, indicating a means of adaptation for HCV to establish a persistent infection. Some special mi RNAs are closely correlated with liver-specific disease progression and the changed levels of mi RNAs are even higher sensitivity and specificity than those of traditional proteins. Therefore, some of them can serve as novel diagnostic/prognostic biomarkers in HCVinfected patients with liver diseases. They are also attractive therapeutic targets for development of new anti-HCV agents.
基金Supported by Grants from 2015 Post-Doc fellowship "Fondazione Umberto Veronesi"(to Gragnani L)2015 AIRC fellowship(to Fognani E)FIRE(to Piluso A)
文摘Not only is chronic hepatitis C virus(HCV) infection a major public health problem,but also it can cause hepatocellular carcinoma and,more rarely,nonHodgkin's lymphoma.These characteristics mean that HCV is the only virus infecting humans that is able to cause two different cancers.The fine pathogenetic and molecular mechanisms by which HCV induces these two malignancies are not completely clear.In the last decade,it has been shown that microRNAs(miRNAs),a class of 21-23-nucleotide molecules modulating posttranscriptional gene expression,make an important contribution to the pathogenesis of several cancers and are also considered highly promising biomarkers.Here,we briefly describe the current knowledge about microRNAs' involvement in HCV-related molecular oncogenesis.We decided to focus our attention on studies fully conducted on ex vivo samples with this specific etiology,and on cultured cell lines partially or completely expressing the HCV genome.Some of the results reported in this review are controversial,possibly because of methodological issues,differences in sampling size and features,and ethnicity of patients.What is certain is that miRNAs play a remarkable role in regulating gene expression during oncogenetic processes and in viral infection.A clear understanding of their effects is fundamental to elucidating the mechanisms underlying virus-induced malignancies.
基金Science and Technology Development Foundation(STDF),Project NO.3457(TC/4/Health/2010/hep-1.6)
文摘BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10^(-3) mm^2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^(-3) mm^2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^(-3) mm^2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.
