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. 2020 Sep;235(9):6218-6229.
doi: 10.1002/jcp.29550. Epub 2020 Feb 24.

miRNA-192 and -215 activate Wnt/β-catenin signaling pathway in gastric cancer via APC

Shiqi Deng  1 , Xiaojing Zhang  1   2   3 , Ying Qin  4 , Wangchun Chen  1 , Hu Fan  1 , Xianling Feng  1 , Jian Wang  5 , Ruibin Yan  6 , Yanqiu Zhao  6 , Yulan Cheng  7 , Yanjie Wei  8 , Xinmin Fan  1 , Hassan Ashktorab  9 , Duane Smoot  10 , Stephen J Meltzer  7 , Song Li  6 , Kuan Li  1 , Yin Peng  1   2 , Zhe Jin  1   2
Affiliations

miRNA-192 and -215 activate Wnt/β-catenin signaling pathway in gastric cancer via APC

Shiqi Deng et al. J Cell Physiol. 2020 Sep.

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.

Keywords: APC; Wnt signaling pathway; gastric cancer; miRNA-192 and -215.

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References

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