MicroRNA-194 acts as a prognostic marker and inhibits proliferation in hepatocellular carcinoma by targeting MAP4K4

MicroRNAs (miRNAs) play a crucial role in cancer development and progression of hepatocellular carcinoma (HCC). In this study, we aimed to analyze the role of microRNA-194 (miR-194) in HCC. We found that miR-194 expression was significantly reduced in HCC and its expression was an independent poor p...

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Veröffentlicht in:International journal of clinical and experimental pathology 2015-01, Vol.8 (10), p.12446-12454
Hauptverfasser: Zhao, Yongli, Li, Fenbao, Zhang, Xizhong, Liu, Aiguang, Qi, Jinsong, Cui, Hongkai, Zhao, Peng
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container_issue 10
container_start_page 12446
container_title International journal of clinical and experimental pathology
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creator Zhao, Yongli
Li, Fenbao
Zhang, Xizhong
Liu, Aiguang
Qi, Jinsong
Cui, Hongkai
Zhao, Peng
description MicroRNAs (miRNAs) play a crucial role in cancer development and progression of hepatocellular carcinoma (HCC). In this study, we aimed to analyze the role of microRNA-194 (miR-194) in HCC. We found that miR-194 expression was significantly reduced in HCC and its expression was an independent poor prognostic factor for HCC patient overall and disease-free survival rate. A significant correlation was observed between miR-194 reduction and unfavourable variables including tumor size (P = 0.0315), histologic grade (P = 0.0038), TNM stage (P = 0.0083), intrahepatic metastasis (P = 0.0184). Overexpression of miR-194 in HCC cell lines HepG2 and Hep3B inhibited cell proliferation by blocking G1-S transition and inducing apoptosis. Mitogen-activated protein kinase 4 (MAP4K4), a potential target gene of miR-194, was inversely correlated with miR-194 expression in HCC tissues and cell lines. Further studies demonstrated that miR-194 regulated the progression of HCC through directly inhibiting the expression of MAP4K4 and the restoration of MAP4K4 expression reversed the inhibitory effects of miR-194 on HCC cell proliferation. Together, our findings indicate that miR-194 may serve as a valuable prognostic marker and promising interventional therapeutic target for HCC.
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In this study, we aimed to analyze the role of microRNA-194 (miR-194) in HCC. We found that miR-194 expression was significantly reduced in HCC and its expression was an independent poor prognostic factor for HCC patient overall and disease-free survival rate. A significant correlation was observed between miR-194 reduction and unfavourable variables including tumor size (P = 0.0315), histologic grade (P = 0.0038), TNM stage (P = 0.0083), intrahepatic metastasis (P = 0.0184). Overexpression of miR-194 in HCC cell lines HepG2 and Hep3B inhibited cell proliferation by blocking G1-S transition and inducing apoptosis. Mitogen-activated protein kinase 4 (MAP4K4), a potential target gene of miR-194, was inversely correlated with miR-194 expression in HCC tissues and cell lines. Further studies demonstrated that miR-194 regulated the progression of HCC through directly inhibiting the expression of MAP4K4 and the restoration of MAP4K4 expression reversed the inhibitory effects of miR-194 on HCC cell proliferation. 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Together, our findings indicate that miR-194 may serve as a valuable prognostic marker and promising interventional therapeutic target for HCC.</description><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Apoptosis - genetics</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Blotting, Western</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Proliferation - genetics</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intracellular Signaling Peptides and Proteins - biosynthesis</subject><subject>Kaplan-Meier Estimate</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - mortality</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Prognosis</subject><subject>Protein-Serine-Threonine Kinases - biosynthesis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Transfection</subject><issn>1936-2625</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkN1KxDAQhYsg7rr6CpJLbwpNk6btjbAs_uGuiuh1mabTbrRNapIK-_ZGXEVhYGDOxzmcOYjmtGQiTkWazaJj516TRNCUJ0fRLBV5mnJG55HbKGnN0_0ypiUnIL0jEIaM1nTaOK8kGcC-oSWgG6L0VtUqMEHuVYsWvDI6nMkWR_BGYt9PPVgiwUqlzQCk3hEPtkOvdEc2y0d-x0-iwxZ6h6f7vYheri6fVzfx-uH6drVcx2MqhI9lngtkDZWUN2VSyzIrZSZQFLJgyGtgHCWlvC1FWzcAtMhrlDxjBbK8KZGxRXTx7TtO9YCNRO0t9NVoVai0qwyo6r-i1bbqzEfFRZGwXASD872BNe8TOl8Nyn11BI1mchXNM5ZQGsiAnv3N-g35-TT7BAeve50</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Zhao, Yongli</creator><creator>Li, Fenbao</creator><creator>Zhang, Xizhong</creator><creator>Liu, Aiguang</creator><creator>Qi, Jinsong</creator><creator>Cui, Hongkai</creator><creator>Zhao, Peng</creator><general>e-Century Publishing Corporation</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150101</creationdate><title>MicroRNA-194 acts as a prognostic marker and inhibits proliferation in hepatocellular carcinoma by targeting MAP4K4</title><author>Zhao, Yongli ; 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subjects Adult
Aged
Animals
Apoptosis - genetics
Biomarkers, Tumor - analysis
Blotting, Western
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - mortality
Carcinoma, Hepatocellular - pathology
Cell Proliferation - genetics
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic - genetics
Heterografts
Humans
Immunohistochemistry
Intracellular Signaling Peptides and Proteins - biosynthesis
Kaplan-Meier Estimate
Liver Neoplasms - genetics
Liver Neoplasms - mortality
Liver Neoplasms - pathology
Male
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs - genetics
Middle Aged
Original
Prognosis
Protein-Serine-Threonine Kinases - biosynthesis
Real-Time Polymerase Chain Reaction
Transfection
title MicroRNA-194 acts as a prognostic marker and inhibits proliferation in hepatocellular carcinoma by targeting MAP4K4
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