miRNA‐192 and ‐215 activate Wnt/β‐catenin signaling pathway in gastric cancer via APC
Shiqi Deng, Xiaojing Zhang, Ying� Qin, Wangchun Chen, Fan Hu, Xianling Feng, Jian Wang, Ruibin Yan, Yanqiu Zhao, Yulan Cheng, Yanjie Wei, Xinmin Fan, Hassan Ashktorab, Duane T. Smoot, Stephen J. Meltzer, Song Li, Kuan Li, Yin Peng, Zhe Jin
Abstract
Although great progress has been made in surgical techniques, traditional radiotherapy, and chemotherapy, gastric cancer (GC) is still the most common malignant tumor and has a high mortality, which highlights the importance of novel diagnostic markers. Emerging studies suggest that different microRNAs (miRNAs) are involved in tumorigenesis of GC. In this study, we found that miRNA-192 and -215 are significantly upregulated in GC and promote cell proliferation and migration. Adenomatous polyposis coli (APC), a well-known negative regulator in Wnt signaling, has been proved to be a target of miRNA-192 and -215. Inhibition of miRNA-192 or -215 reduced the Topflash activities and repressed the expression of Wnt signaling pathway proteins, while APC small interfering RNAs reversed the inhibitory effects, suggesting that miRNA-192 and -215 activate Wnt signaling via APC. In addition, APC mediates the cell proliferation and migration regulated by miRNA-192 and -215. Furthermore, APC is downregulated in GC tissues and negatively correlated with the expression of miRNA-192 and -215. In summary, miRNA-192 and -215 target APC and function as oncogenic miRNAs by activating Wnt signaling in GC, revealing to be potential therapeutic targets.