TRPM2-AS 通过调控 TAF15 促进癌细胞增殖。
TRPM2-AS promotes cancer cell proliferation through control of TAF15.
机构信息
Radiotherapy Department, Sichuan Cancer Hospital & Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Gastroenterology and Hepatology, Academy of Medical Sciences and Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China.
出版信息
Int J Biochem Cell Biol. 2020 Mar;120:105683. doi: 10.1016/j.biocel.2019.105683. Epub 2019 Dec 27.
BACKGROUND
Colorectal cancer (CRC) ranks the third among all common malignancy worldwide. Long noncoding RNAs (lncRNAs) have been demonstrated as implicated in CRC, but the roles of many lncRNAs in CRC remain unclear. Exploration of lncRNA TRMP2-AS and its nearby gene in CRC progress was the focus of current study.
METHODS
The expression of TRPM2-AS and its nearby mRNA TRPM2 was measured by using RT-qPCR. The protein levels of TRPM2 and TAF15 were determined using western blot. Cell proliferation was detected by using CCK-8, colony formation and EdU assays. The interaction between TAF15 and TRPM2-AS or TRPM2 was evaluated by RNA pull-down and RIP assays. The TRPM2 mRNA stability was probed using the transcriptional inhibitor Actinomycin D.
RESULTS
TRPM2-AS was significantly upregulated in CRC cells. Knock-down of TRPM2-AS inhibited CRC cell proliferation. Mechanically, TRPM2-AS directly interacted with RNA-binding protein (RBP) TAF15 and thus maintained the mRNA stability of TRPM2. TRPM2 was a prerequisite for TRPM2-AS to exert its promoting function in CRC cell proliferation.
CONCLUSION
This research demonstrated that TRPM2-AS facilitated proliferation of CRC cells by enhancing TAF15-mediated mRNA stability of TRPM2, unmasking the role of TRPM2-AS in CRC.
背景
结直肠癌（CRC）在全球所有常见恶性肿瘤中排名第三。长链非编码 RNA（lncRNA）已被证明与 CRC 有关，但许多 lncRNA 在 CRC 中的作用仍不清楚。本研究聚焦于 lncRNA TRMP2-AS 及其附近基因在 CRC 进展中的作用。
方法
采用 RT-qPCR 检测 TRPM2-AS 及其附近 mRNA TRPM2 的表达。采用 Western blot 检测 TRPM2 和 TAF15 的蛋白水平。采用 CCK-8、集落形成和 EdU 检测细胞增殖。采用 RNA 下拉和 RIP 实验评估 TAF15 与 TRPM2-AS 或 TRPM2 的相互作用。采用转录抑制剂 Actinomycin D 探测 TRPM2 mRNA 的稳定性。
结果
TRPM2-AS 在 CRC 细胞中显著上调。敲低 TRPM2-AS 抑制 CRC 细胞增殖。机制上，TRPM2-AS 直接与 RNA 结合蛋白（RBP）TAF15 相互作用，从而维持 TRPM2 的 mRNA 稳定性。TRPM2 是 TRPM2-AS 在 CRC 细胞增殖中发挥促进作用的前提。
结论
本研究表明，TRPM2-AS 通过增强 TAF15 介导的 TRPM2 mRNA 稳定性促进 CRC 细胞增殖，揭示了 TRPM2-AS 在 CRC 中的作用。
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