Hua Hong-Wei, Jiang Feng, Huang Qian, Liao Zhijun, Ding Gang
Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai 202150, China.
Oncotarget. 2015 Feb 28;6(6):3840-7. doi: 10.18632/oncotarget.2927.
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.
Wnt/β-连环蛋白信号通路的持续激活在包括肝细胞癌（HCC）在内的人类癌症发展中起着关键作用。在此，我们进行了一项基于微小RNA的基因筛选，结果揭示了由微小RNA-153（miR-153）触发的β-连环蛋白信号通路的一种新分支。miR-153的过表达能够促进β-连环蛋白的转录活性，导致肝癌细胞的细胞周期进程、增殖和集落形成。此外，在小鼠肝癌模型中，全身性给予miR-153反义寡核苷酸可抑制肝细胞癌的发生。在分子水平上，我们发现miR-153通过靶向肿瘤抑制因子及β-连环蛋白信号通路抑制剂WWOX的3'-非翻译区来抑制其蛋白水平。因此，我们的研究突出了微小RNA-153/WWOX/β-连环蛋白调控轴在肝癌发生中的重要性。
