The lncRNA XIST/miR‐125b‐2‐3p axis modulates cell proliferation and chemotherapeutic sensitivity via targeting Wee1 in colorectal cancer

作者：Zhao-Lei Zeng, Jia-Huan Lu, Yun Wang, Hui Sheng, Ying‐nan Wang, Zhan‐Hong Chen, Qi‐Nian Wu, Jia‐Bo Zheng, Yan‐Xing Chen, Dong-Dong Yang, Kai Yu, Hai‐Yu Mo, Jia‐jia Hu, Pei‐shan Hu, Zexian Liu, Huai‐Qiang Ju, Rui‐Hua Xu · 发表于：Cancer Medicine · 年份：2021 · DOI：10.1002/cam4.3777 · 被引用次数：33 · 研究领域：Cancer-related molecular mechanisms research、Circular RNAs in diseases、MicroRNA in disease regulation

BACKGROUND: Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR-125b-2-3p, has been identified for predicting chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR-125b-2-3p in advanced CRC under chemotherapy have yet to be elucidated. METHODS: MiR-125b-2-3p expression was detected by real-time PCR (RT-PCR) in CRC tissues. The effects of miR-125b-2-3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR-125b-2-3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on. RESULTS: MiR-125b-2-3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR-125b-2-3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR-125b-2-3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR-125b-2-3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR-125b-2-3p inhibited the proliferation and epithelial-mesenchymal transition (EMT) of CRC induced by lncRNA XIST. CONCLUSIONS: Lower miR-125b-2-3p expr...