Department of Gastroenterology, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510130, P.R. China.
Department of Hospital Infection Control, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510130, P.R. China.
Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2021.11850. Epub 2021 Jan 26.
Long non-coding RNAs (lncRNAs) serve a key role in different types of cancer, including colorectal cancer (CRC). The exact roles and mechanisms underlying lncRNA00963 [long intergenic non‑protein coding RNA 963 (LINC00963)] in CRC are not completely understood. The present study aimed to identify the effects and mechanisms underlying LINC00963 in CRC. Firstly, the LINC00963 expression was detected using reverse transcription‑quantitative PCR and the results demonstrated that LINC00963 expression levels were significantly increased in CRC tissues and cell lines compared with healthy tissues and HpoEpiC cells, respectively. Online database analysis indicated that high levels of LINC00963 were associated with low survival rates. The results of functional experiments, such as CCK‑8 assay, colony formation assay, wound healing assay and Transwell invasion assay, indicated that LINC00963 knockdown significantly inhibited CRC cell proliferation, colony formation, migration and invasion compared with the small interfering RNA (si)‑negative control (NC) group. Furthermore, the luciferase reporter indicated that LINC00963 competitively regulated microRNA (miR)‑10b by targeting fibroblast growth factor 13 (FGF13). Compared with si‑NC, LINC00963 knockdown decreased the expression levels of FGF13, vimentin and N‑cadherin, and increased the expression of E‑cadherin as detecting by western blotting. miR‑10b inhibitors partly attenuated si‑LINC00963‑induced inhibition of CRC cell proliferation, migration and invasion. Collectively, the results of the present study suggested a potential role of the LINC00963/miR-10b/FGF13 axis in the tumorigenesis and progression of CRC, indicating a novel lncRNA-based diagnostic or therapeutic target for CRC.
长链非编码 RNA(lncRNA)在包括结直肠癌(CRC)在内的多种癌症中发挥着关键作用。lncRNA00963[长基因间非蛋白编码 RNA 963(LINC00963)]在 CRC 中的确切作用和机制尚不完全清楚。本研究旨在确定 LINC00963 在 CRC 中的作用及其机制。首先,通过逆转录定量 PCR 检测 LINC00963 的表达,结果表明,与健康组织和 HpoEpiC 细胞相比,CRC 组织和细胞系中 LINC00963 的表达水平显著升高。在线数据库分析表明,高水平的 LINC00963 与低生存率相关。CCK-8 测定、集落形成测定、划痕愈合测定和 Transwell 侵袭测定等功能实验的结果表明,与 siRNA 阴性对照(NC)组相比,LINC00963 敲低显著抑制 CRC 细胞增殖、集落形成、迁移和侵袭。此外,荧光素酶报告基因表明,LINC00963 通过靶向成纤维细胞生长因子 13(FGF13)竞争性调节 microRNA(miR)-10b。与 si-NC 相比,LINC00963 敲低降低了 FGF13、波形蛋白和 N-钙粘蛋白的表达水平,Western blot 检测结果表明 E-钙粘蛋白的表达水平升高。miR-10b 抑制剂部分减弱了 si-LINC00963 诱导的 CRC 细胞增殖、迁移和侵袭抑制作用。综上所述,本研究结果提示 LINC00963/miR-10b/FGF13 轴在 CRC 发生和进展中的潜在作用,表明该轴是 CRC 新型基于 lncRNA 的诊断或治疗靶点。