Wu Hongyu, Tao Yangbao, Zhang Weiyuan, Wang Guiyu, Zhang Qian
Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11939. Epub 2021 Mar 2.
Colorectal cancer (CRC) is a lethal and common malignancy worldwide. Non‑coding (nc)RNAs have been shown to modulate tumor progression in several types of cancer. The present study aimed to investigate the role of hsa_circ_0000212 in CRC, as a sponge of microRNA (miR)‑491. The expression levels of miR‑491 and forkhead box P4 (FOXP4) were analyzed using data from The Cancer Genome Atlas. The association between miR‑491 and FOXP4 and the clinicopathological characteristics were also analyzed. A novel circular (circ)RNA, hsa_circ_0000212, was found to sponge miR‑491 based on bioinformatics analysis. The potential binding site between miR‑491 and FOXP4 or circ‑0000212 was validated using luciferase and RNA immunoprecipitation assays. The expression levels and distribution of circ‑0000212 was also determined. Cell Counting Kit‑8 and colony formation assays were performed to determine the role of miR‑491 or circ‑0000212 on the proliferation of the CRC cells. Decreased miR‑491 or increased FOXP4 expression levels were associated with the pathological stage in patients with CRC. In addition, miR‑491 inhibited cell proliferation by targeting FOXP4. circ‑0000212 was increased in CRC tissues and was predominantly localized in the cytoplasm. Furthermore, circ‑0000212 augmented viability of the CRC cells by sponging miR‑491 and modulating FOXP4. In conclusion, circ‑0000212 may serve as a novel tumor‑promoter and drug target in CRC.
结直肠癌（CRC）是全球范围内一种致命且常见的恶性肿瘤。非编码（nc）RNA已被证明可调节多种癌症类型中的肿瘤进展。本研究旨在探讨hsa_circ_0000212作为微小RNA（miR）-491的海绵在结直肠癌中的作用。使用来自癌症基因组图谱的数据分析了miR-491和叉头框P4（FOXP4）的表达水平。还分析了miR-491与FOXP4之间的关联以及临床病理特征。基于生物信息学分析发现一种新型环状（circ）RNA，hsa_circ_0000212，可作为miR-491的海绵。使用荧光素酶和RNA免疫沉淀试验验证了miR-491与FOXP4或circ-0000212之间的潜在结合位点。还确定了circ-0000212的表达水平和分布。进行细胞计数试剂盒-8和集落形成试验以确定miR-491或circ-0000212对结直肠癌细胞增殖的作用。miR-491表达降低或FOXP4表达增加与结直肠癌患者的病理分期相关。此外，miR-491通过靶向FOXP4抑制细胞增殖。circ-0000212在结直肠癌组织中表达增加，且主要定位于细胞质中。此外，circ-0000212通过海绵化miR-491和调节FOXP4增强了结直肠癌细胞的活力。总之，circ-0000212可能作为结直肠癌中一种新型的肿瘤促进因子和药物靶点。
