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MicroRNA-153 promotes Wnt/?-catenin activation in hepatocellular carcinoma through suppression of WWOX.

ABSTRACT: Persistent activation of Wnt/?-catenin signaling plays crucial roles in the development of human cancers, including hepatocellular carcinoma (HCC). Here, we performed a MicroRNA-based genetic screen, which revealed a novel diversion in ?-catenin signaling triggered by MicroRNA-153 (miR-153). Overexpression of miR-153 was able to promote ?-catenin transcriptional activity, leading to cell-cycle progression, proliferation and colony formation of HCC cells. Additionally, systemic administration of miR-153 antigomir suppressed hepatocellular carcinogenesis in a murine liver cancer model. At the molecular level, we found that miR-153 inhibited protein level of WWOX, a tumor suppressor and inhibitor of ?-catenin signaling, through targeting its 3'-untranslated region. Therefore, our study highlights the importance of MicroRNA-153/WWOX/?-catenin regulatory axis in the HCC tumorigenesis.

SUBMITTER: Hua HW

PROVIDER: S-EPMC4414157 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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MicroRNA-153 promotes Wnt/β-catenin activation in hepatocellular carcinoma through suppression of WWOX.

Hua Hong-Wei HW Jiang Feng F Huang Qian Q Liao Zhijun Z Ding Gang G

Oncotarget 20150201 6

Persistent activation of Wnt/β-catenin signaling plays crucial roles in the development of human cancers, including hepatocellular carcinoma (HCC). Here, we performed a MicroRNA-based genetic screen, which revealed a novel diversion in β-catenin signaling triggered by MicroRNA-153 (miR-153). Overexpression of miR-153 was able to promote β-catenin transcriptional activity, leading to cell-cycle progression, proliferation and colony formation of HCC cells. Additionally, systemic administration of ...[more]

PMID: 25708809

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