Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of General Surgery, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, China.
J Transl Med. 2022 Jan 31;20(1):58. doi: 10.1186/s12967-022-03240-x.
Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms.
Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1).
It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level.
Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.
结肠癌是一种常见的消化道恶性肿瘤，其发病率在胃肠道肿瘤中位居第三。本研究旨在探讨一种新型环状 RNA（circCSPP1）在结肠癌中的作用及其潜在的分子机制。
采用生物信息学分析和逆转录定量 PCR 检测结肠癌组织和细胞系中 circCSPP1 的表达水平。通过 CCK-8、Transwell 和集落形成实验研究 circCSPP1 对结肠癌细胞行为的影响。通过生物信息学分析以及荧光原位杂交和 RNA 下拉实验揭示 circCSPP1 与 microRNA（miR）-431、Rho 相关卷曲螺旋蛋白激酶 1（ROCK1）和锌指 E 框结合同源盒 1（ZEB1）之间的相互作用。
发现 circCSPP1 在结肠癌组织和细胞系中表达显著上调。circCSPP1 的过表达显著促进了结肠癌细胞的增殖、迁移和侵袭，而 circCSPP1 的沉默则产生相反的效果。机制上，circCSPP1 被发现与 miR-431 结合。此外，ROCK1 和 ZEB1 被鉴定为 miR-431 的靶基因。进一步的挽救实验证实了 circCSPP1、miR-431、ROCK1 和 ZEB1 之间的相互作用。此外，circCSPP1 促进了 ROCK1、细胞周期蛋白 D1、细胞周期蛋白依赖性激酶 4、ZEB1 和 Snail 的表达水平，并降低了 E-钙黏蛋白的表达水平。
综上所述，本研究结果表明，circCSPP1 可能通过调节 miR-431/ROCK1 和 miR-431/ZEB1 信号通路在结肠癌的进展中作为竞争性内源性 RNA 发挥作用。
