The role of microRNAs in liver cancer progression

Primary liver cancer, predominantly consisting of hepatocellular carcinoma (HCC), is one of the most common and aggressive human malignancies worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression post-transcriptionally. Emerging evidence indicates that miRNAs are often deregulated in HCC, and that some specific miRNAs are associated with the clinicopathological features of HCC. Recent work demonstrates that miRNAs have essential roles in HCC progression and directly contribute to cell proliferation, avoidance of apoptotic cell death, and metastasis of HCC by targeting a large number of critical protein-coding genes. The discovery of the aberrantly expressed miRNAs and their corresponding targets has opened a novel avenue to investigate the molecular mechanism of HCC progression and to develop potential therapeutics against HCC. In this review, we summarise current knowledge about the roles and validated targets of miRNAs in liver cancer progression.

[1]  J. Yun,et al.  Effects of MicroRNA‐29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma , 2009, Hepatology.

[2]  X. Wang,et al.  Let-7g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. , 2010, Journal of hepatology.

[3]  J. Mott MicroRNAs involved in tumor suppressor and oncogene pathways: Implications for hepatobiliary neoplasia , 2009, Hepatology.

[4]  S. Giulini,et al.  MicroRNA‐23b mediates urokinase and c‐met downmodulation and a decreased migration of human hepatocellular carcinoma cells , 2009, The FEBS journal.

[5]  Reuven Agami,et al.  Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. , 2007, The EMBO journal.

[6]  Guobin Wang,et al.  MicroRNA-602 regulating tumor suppressive gene RASSF1A is over-expressed in hepatitis B virus-infected liver and hepatocellular carcinoma , 2010, Cancer biology & therapy.

[7]  Jen-Leih Wu,et al.  miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines. , 2008, Biochemical and biophysical research communications.

[8]  Gian Luca Grazi,et al.  MicroRNA-221 Targets Bmf in Hepatocellular Carcinoma and Correlates with Tumor Multifocality , 2009, Clinical Cancer Research.

[9]  H. El‐Serag,et al.  Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. , 2007, Gastroenterology.

[10]  L. Lim,et al.  MicroRNAs in the miR-106b Family Regulate p21/CDKN1A and Promote Cell Cycle Progression , 2008, Molecular and Cellular Biology.

[11]  K. Choy,et al.  MiR-222 Overexpression Confers Cell Migratory Advantages in Hepatocellular Carcinoma through Enhancing AKT Signaling , 2010, Clinical Cancer Research.

[12]  S. Lowe,et al.  miR-221 overexpression contributes to liver tumorigenesis , 2009, Proceedings of the National Academy of Sciences.

[13]  Yi Tie,et al.  miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. , 2009, Cancer letters.

[14]  C. Croce,et al.  MicroRNA signatures in human cancers , 2006, Nature Reviews Cancer.

[15]  Shuhan Sun,et al.  miR‐17‐5p Promotes migration of human hepatocellular carcinoma cells through the p38 mitogen‐activated protein kinase‐heat shock protein 27 pathway , 2010, Hepatology.

[16]  H. Kung,et al.  Hsa‐let‐7g inhibits proliferation of hepatocellular carcinoma cells by downregulation of c‐Myc and upregulation of p16INK4A , 2011, International journal of cancer.

[17]  Jian-Rong Yang,et al.  MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. , 2009, Cancer research.

[18]  Thomas D. Schmittgen,et al.  Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis. , 2008, Cancer research.

[19]  J. Inazawa,et al.  Abstract 2080: miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma , 2010 .

[20]  T. Patel,et al.  MicroRNA expression profiling: A molecular tool for defining the phenotype of hepatocellular tumors , 2008, Hepatology.

[21]  C. Croce,et al.  MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells. , 2010, Cancer research.

[22]  Yang Li,et al.  Role of the miR‐106b‐25 microRNA cluster in hepatocellular carcinoma , 2009, Cancer science.

[23]  Shinji Tanaka,et al.  miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. , 2010, Carcinogenesis.

[24]  Kathryn A. O’Donnell,et al.  Therapeutic microRNA Delivery Suppresses Tumorigenesis in a Murine Liver Cancer Model , 2009, Cell.

[25]  X. Zhang,et al.  MicroRNA‐122 might be a double‐edged sword in hepatocellular carcinoma , 2009, Hepatology.

[26]  Ming Yao,et al.  Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA , 2010, Nature Cell Biology.

[27]  Ming Yao,et al.  MicroRNA‐30d promotes tumor invasion and metastasis by targeting Galphai2 in hepatocellular carcinoma , 2010, Hepatology.

[28]  K. Ghoshal,et al.  MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. , 2007, Gastroenterology.

[29]  K. Ghoshal,et al.  TGFβ mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3 , 2009, Oncogene.

[30]  Hsien-Da Huang,et al.  MicroRNA‐122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma , 2009, Hepatology.

[31]  Leina Ma,et al.  Expression of miR-122 mediated by adenoviral vector induces apoptosis and cell cycle arrest of cancer cells. , 2010, Cancer biology & therapy.

[32]  Nathalie Wong,et al.  MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. , 2008, Gastroenterology.

[33]  Ding‐Shinn Chen,et al.  MicroRNA-18a prevents estrogen receptor-alpha expression, promoting proliferation of hepatocellular carcinoma cells. , 2009, Gastroenterology.

[34]  Laura Pelletier,et al.  MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations , 2008, Hepatology.

[35]  K. Ghoshal,et al.  MicroRNA-122 Inhibits Tumorigenic Properties of Hepatocellular Carcinoma Cells and Sensitizes These Cells to Sorafenib* , 2009, The Journal of Biological Chemistry.

[36]  Kuo-Bin Li,et al.  Profiling MicroRNA Expression in Hepatocellular Carcinoma Reveals MicroRNA-224 Up-regulation and Apoptosis Inhibitor-5 as a MicroRNA-224-specific Target* , 2008, Journal of Biological Chemistry.

[37]  Rajagopal N. Aravalli,et al.  Molecular mechanisms of hepatocellular carcinoma , 2008, Hepatology.

[38]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[39]  Shuhan Sun,et al.  Up‐regulated microRNA‐143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression , 2009, Hepatology.

[40]  C. Croce,et al.  MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma , 2008, Oncogene.

[41]  C. Croce,et al.  Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. , 2007, Cancer research.

[42]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[43]  Lin He,et al.  MicroRNAs: small RNAs with a big role in gene regulation , 2004, Nature Reviews Genetics.

[44]  C. Croce,et al.  MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. , 2009, Cancer research.

[45]  Y. Doki,et al.  The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma. , 2010, Journal of hepatology.

[46]  Ronald A. DePinho,et al.  Hepatocellular carcinoma pathogenesis: from genes to environment , 2006, Nature Reviews Cancer.

[47]  J. Yun,et al.  MicroRNA‐195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells , 2009, Hepatology.

[48]  Reuven Agami,et al.  Regulation of the p27Kip1 tumor suppressor by miR‐221 and miR‐222 promotes cancer cell proliferation , 2007 .

[49]  Hansjuerg Alder,et al.  miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. , 2009, Cancer cell.

[50]  Yi Tie,et al.  MicroRNA‐101 regulates expression of the v‐fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma , 2009, Hepatology.

[51]  S. Thorgeirsson,et al.  Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties , 2009, Oncogene.

[52]  Angela M. Liu,et al.  MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties. , 2010, Biochemical and biophysical research communications.