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Underexpressed microRNA-199b-5p targets Hypoxia-Inducible Factor-1α in hepatocellular carcinoma and predicts prognosis of hepatocellular carcinoma patients.
- Source :
- Journal of Gastroenterology & Hepatology; Nov2011, Vol. 26 Issue 11, p1630-1637, 8p, 1 Diagram, 2 Charts, 4 Graphs
- Publication Year :
- 2011
-
Abstract
- Background and Aim: MicroRNAs are short noncoding RNA molecules that are responsible for the posttranscriptional regulation of target genes. The aim of this study was to determine whether microRNA-199b-5p (miR-199b) plays a role in the progression and prognosis of hepatocellular carcinoma (HCC), and to elucidate whether hypoxia-inducible factor-1α (Hif1α) is regulated by miR-199b. Methods: In this study, 35 matched HCCs and cirrhosis tissues were assayed for miR-199b and Hif1α expression. To evaluate the role of miR-199b, we assessed cell proliferation rate and clonogenic survival of miR-199b- or negative control-transfected cells by MTT and clone formation assay, respectively. In addition, the regulation of Hif1α by miR-199b was evaluated by Western blotting and luciferase assay. MiR-199b was downregulated in 77% of HCCs, whereas Hif1α protein was upregulated in 69% of cases. A significant inverse correlation between miR-199b and Hif1α was observed in HCCs. Results: Patients with lower levels of miR-199b expression had poorer overall survival and progression-free survival rates, whereas patients with higher levels of miR-199b expression had better survival. Moreover, miR-199b could restrain cell growth and obviously enhance the radiosensitizing effect of HepG2 cells. MiR-199b and pGL3-Hif1α vector-transfected cells showed suppressed Hif1α protein expression and significant reduced luciferase activity. Conclusions: Underexpressed miR-199b, which may be via the upregulation of Hif1α in HCCs, is inversely correlated with survival and directly correlated with the malignant status of HCC patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08159319
- Volume :
- 26
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Journal of Gastroenterology & Hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 66694967
- Full Text :
- https://doi.org/10.1111/j.1440-1746.2011.06758.x