MicroRNA-153 promotes Wnt/β-catenin activation in hepatocellular carcinoma through suppression of WWOX
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Hong-Wei Hua1,*, Feng Jiang2,*, Qian Huang2, Zhijun Liao2, Gang Ding2
1Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
2Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai 202150, China
*These authors have contributed equally to this work
Gang Ding, e-mail: [email protected]
Keywords: Hepatocellular carcinoma, β-catenin, MicroRNA, MicroRNA-153, WWOX
Received: September 19, 2014 Accepted: December 16, 2014 Published: February 02, 2015
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 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 β-catenin signaling, through targeting its 3'-untranslated region. Therefore, our study highlights the importance of MicroRNA-153/WWOX/β-catenin regulatory axis in the HCC tumorigenesis.
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