4.5 Article

microRNA-622 acts as a tumor suppressor in hepatocellular carcinoma

Journal

CANCER BIOLOGY & THERAPY
Volume 16, Issue 12, Pages 1754-1763

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2015.1095402

Keywords

hepatocellular carcinoma; MAP4K4; microRNA; miR-622; therapeutic target

Categories

Funding

  1. National Nature Science Foundation of China [81072020, 81172311, 30973458]
  2. '085' and Integrated Traditional Chinese and Western Medicine first-class discipline construction of science and technology innovation in Shanghai University of Traditional Chinese Medicine [085ZY1220]

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microRNAs (miRNAs) are important regulators of tumor development and progression. In this study, we aimed to explore the expression and role of miR-622 in hepatocellular carcinoma (HCC). We found that miR-622 was significantly downregulated in human HCC specimens compared to adjacent noncancerous liver tissues. miR-622 downregulation was significantly associated with aggressive parameters and poor prognosis in HCC. Enforced expression of miR-622 significantly decreased the proliferation and colony formation and induced apoptosis of HCC cells. In vivo studies demonstrated that miR-622 overexpression retarded the growth of HCC xenograft tumors. Bioinformatic analysis and luciferase reporter assays revealed that miR-622 directly targeted the 3'-untranslated region (UTR) of mitogen-activated protein 4 kinase 4 (MAP4K4) mRNA. Ectopic expression of miR-622 led to a significant reduction of MAP4K4 expression in HCC cells and xenograft tumors. Overexpression of MAP4K4 partially restored cell proliferation and colony formation and reversed the induction of apoptosis in miR-622-overexpressing HCC cells. Inhibition of JNK and NF-kappa B signaling phenocopied the anticancer effects of miR-622 on HCC cells. Taken together, miR-622 acts as a tumor suppressor in HCC and restoration of miR-622 may provide therapeutic benefits in the treatment of HCC.

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