Yu Chao, Li Deguan, Yan Qiang, Wang Yigao, Yang Xiaodong, Zhang Shangxin, Zhang Yonghong, Zhang Zhen
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China.
Cancer Manag Res. 2021 Mar 11;13:2295-2306. doi: 10.2147/CMAR.S281377. eCollection 2021.
Colorectal cancer (CRC) is one of the most common aggressive neoplasms worldwide. Circular RNAs (circRNAs) have been involved in the biological process of CRC. This study aimed to explore the effects of circ_0005927 on CRC progression and underneath mechanism.
The expression of circ_0005927, microRNA-942-5p (miR-942-5p) and basic leucine zipper ATF-like transcription factor 2 (BATF2) was detected by quantitative real time polymerase chain reaction (qRT-PCR). The protein expression of BATF2 was determined by Western blot. The effects among circ_0005927, miR-942-5p and BATF2 on cell colony-forming ability, apoptosis and migratory and invasive abilities were revealed by cell colony formation, flow apoptosis and transwell assays, respectively. The associated relationship between miR-942-5p and circ_0005927 or BATF2 was predicted by Circinteractome or TargetScan online database, and identified by dual-luciferase reporter or RNA immunoprecipitation (RIP) assay. The impacts of circ_0005927 overexpression on tumor growth in vivo were investigated by in vivo tumor formation assay.
Circ_0005927 expression and the mRNA and protein expression of BATF2 were dramatically downregulated, while miR-942-5p expression was obviously upregulated in CRC tissues or cells compared with control groups. Circ_0005927 overexpression repressed cell colony-forming ability, migration and invasion, whereas induced cell apoptosis in CRC; however, these impacts were hindered by miR-942-5p mimic or BATF2 knockdown. Furthermore, circ_0005927 was a sponge of miR-942-5p, and miR-942-5p bound to BATF2. In addition, circ_0005927 overexpression repressed tumor growth in vivo.
Circ_0005927 suppressed cell colony-forming ability, migration and invasion, and promoted cell apoptosis by sponging miR-942-5p to induce BATF2 in CRC. The possible mechanism provides a theoretical basis for the study of circRNA-directed therapy for CRC.
结直肠癌（CRC）是全球最常见的侵袭性肿瘤之一。环状RNA（circRNAs）参与了结直肠癌的生物学过程。本研究旨在探讨circ_0005927对结直肠癌进展的影响及其潜在机制。
采用定量实时聚合酶链反应（qRT-PCR）检测circ_0005927、微小RNA-942-5p（miR-942-5p）和碱性亮氨酸拉链ATF样转录因子2（BATF2）的表达。通过蛋白质印迹法测定BATF2的蛋白表达。分别通过细胞集落形成、流式细胞凋亡和Transwell实验揭示circ_0005927、miR-942-5p和BATF2对细胞集落形成能力、凋亡以及迁移和侵袭能力的影响。通过Circinteractome或TargetScan在线数据库预测miR-942-5p与circ_0005927或BATF2之间的关联关系，并通过双荧光素酶报告基因或RNA免疫沉淀（RIP）实验进行验证。通过体内肿瘤形成实验研究circ_0005927过表达对体内肿瘤生长的影响。
与对照组相比，结直肠癌组织或细胞中circ_0005927的表达以及BATF2的mRNA和蛋白表达显著下调，而miR-942-5p的表达明显上调。circ_0005927过表达抑制了结直肠癌细胞的集落形成能力、迁移和侵袭能力，同时诱导细胞凋亡；然而，miR-942-5p模拟物或BATF2敲低可阻碍这些影响。此外，circ_0005927是miR-942-5p的海绵，且miR-942-5p与BATF2结合。另外，circ_0005927过表达抑制了体内肿瘤生长。
circ_0005927通过吸附miR-942-5p诱导BATF2，从而抑制结直肠癌细胞的集落形成能力、迁移和侵袭能力，并促进细胞凋亡。这一可能机制为结直肠癌的circRNA导向治疗研究提供了理论依据。
