Gu Chao, Zou Shitao, He Chao, Zhou Jundong, Qu Rui, Wang Qin, Qi Jie, Zhou Ming, Yan Shuai, Ye Zhenyu
Gastrointestinal Surgery Department, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China.
Suzhou Cancer Center Core Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China.
Exp Ther Med. 2020 Apr;19(4):2543-2550. doi: 10.3892/etm.2020.8518. Epub 2020 Feb 11.
Increasing evidence has demonstrated that long non-coding (lnc) RNA is aberrantly expressed in numerous types of cancer. Colorectal cancer is a common malignancy; however, the role and mechanism underlying the influence of lncRNA-colon cancer associated transcript 1 (CCAT1) in colorectal cancer is yet to be elucidated. The present study revealed that CCAT1 is highly expressed in colorectal cancer tissues. Bioinformatics analysis and a dual-luciferase reporter gene assay indicated that CCAT1 and microRNA (miR)-218 had complementary binding sites. Furthermore, reverse transcription-quantitative PCR revealed that miR-218 was downregulated in colorectal cancer tissues compared with paired adjacent healthy tissues. To investigate the biological effects of CCAT1 on colorectal cancer cells, MTT and Transwell assays were performed. The results revealed that when compared with the control group, CCAT1-short hairpin (sh)RNA significantly inhibited colorectal cancer cell (SW480) viability and decreased migration and invasiveness. In addition, CCAT1-shRNA significantly reduced vascular endothelial growth factor (VEGF) expression in SW480 cells; however, these effects were partially rescued by an miR-218 inhibitor. Furthermore, it was revealed that the CCAT1-plasmid significantly promoted the viability of SW480 cells, increased cell migration and invasiveness, and significantly increased VEGF expression. However, these effects were also partially rescued by with a miR-218 mimic. Taken together, the present results identified that the CCAT1/miR-218 axis serves a key role in the regulation of colorectal cancer progression, which may be used as potential therapeutic target for the treatment of colorectal cancer.
越来越多的证据表明，长链非编码（lnc）RNA在多种类型的癌症中异常表达。结直肠癌是一种常见的恶性肿瘤；然而，lncRNA-结肠癌相关转录本1（CCAT1）在结直肠癌中的作用及潜在机制尚待阐明。本研究表明，CCAT1在结直肠癌组织中高表达。生物信息学分析和双荧光素酶报告基因检测表明，CCAT1与微小RNA（miR）-218具有互补结合位点。此外，逆转录定量PCR显示，与配对的相邻健康组织相比，miR-218在结直肠癌组织中表达下调。为了研究CCAT1对结直肠癌细胞的生物学作用，进行了MTT和Transwell检测。结果显示，与对照组相比，CCAT1短发夹（sh）RNA显著抑制结直肠癌细胞（SW480）的活力，并降低其迁移和侵袭能力。此外，CCAT1-shRNA显著降低SW480细胞中血管内皮生长因子（VEGF）的表达；然而，这些作用被miR-218抑制剂部分挽救。此外，研究发现CCAT1质粒显著促进SW480细胞的活力，增加细胞迁移和侵袭能力，并显著增加VEGF表达。然而，这些作用也被miR-218模拟物部分挽救。综上所述，本研究结果表明，CCAT1/miR-218轴在结直肠癌进展的调控中起关键作用，这可能作为结直肠癌治疗的潜在靶点。
