Dong Xinhua, Yang Zhen, Yang Hongwei, Li Dongyan, Qiu Xinguang
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Oncol. 2020 Feb 20;10:160. doi: 10.3389/fonc.2020.00160. eCollection 2020.
Long non-coding RNAs (lncRNAs) are critical to colorectal cancer (CRC) progression. In the current study, the objective was the exploration of the role played by lncRNA MIR4435-2HG in CRC proliferation and metastasis. lncRNA MIR4435-2HG expression and its association with CRC were analyzed using database and clinical specimens. The influences exerted by MIR4435-2HG on cell proliferating process, invading process, and migrating process of CRC were identified after MIR4435-2HG knockdown. The influences exerted by MIR4435-2HG on tumor growth and metastasis were assessed . The underlying mechanistic associations between MIR4435-2HG, microRNA miR-206, and the transcription factor Yes-associated protein 1 (YAP1) were assessed using bioinformatics and a luciferase reporter gene assay. MIR4435-2HG was highly expressed in CRC tissue in contrast with that in regular tissues and displayed relations to poor prognosis. MIR4435-2HG knockdown could suppress CRC cell proliferation, invasion, and migration. Moreover, MIR4435-2HG knockdown inhibited CRC growth and liver metastasis . We found MIR4435-2HG knockdown reduced YAP1, CTGF, AREG, vimentin, Snail, Slug, and Twist expression but enhanced E-cadherin expression. Functionally, MIR4435-2HG acted as a competing endogenous RNA (ceRNA) to upregulate YAP1 by sponging miR-206. MIR4435-2HG promoted CRC growth and metastasis through miR-206/YAP1 axis and is likely to play prognostic marker roles and be therapeutically targeted in CRC.
长链非编码RNA（lncRNAs）对结直肠癌（CRC）的进展至关重要。在本研究中，目的是探讨lncRNA MIR4435-2HG在CRC增殖和转移中所起的作用。使用数据库和临床标本分析lncRNA MIR4435-2HG的表达及其与CRC的关联。在敲低MIR4435-2HG后，确定其对CRC细胞增殖过程、侵袭过程和迁移过程的影响。评估MIR4435-2HG对肿瘤生长和转移的影响。使用生物信息学和荧光素酶报告基因检测评估MIR4435-2HG、微小RNA miR-206和转录因子Yes相关蛋白1（YAP1）之间潜在的机制关联。与正常组织相比，MIR4435-2HG在CRC组织中高表达，且与预后不良相关。敲低MIR4435-2HG可抑制CRC细胞的增殖、侵袭和迁移。此外，敲低MIR4435-2HG可抑制CRC的生长和肝转移。我们发现敲低MIR4435-2HG可降低YAP1、结缔组织生长因子（CTGF）、双调蛋白（AREG）、波形蛋白、蜗牛蛋白（Snail）、蛞蝓蛋白（Slug）和Twist的表达，但增强E-钙黏蛋白的表达。在功能上，MIR4435-2HG作为竞争性内源RNA（ceRNA），通过海绵吸附miR-206上调YAP1。MIR4435-2HG通过miR-206/YAP1轴促进CRC的生长和转移，可能在CRC中发挥预后标志物作用并成为治疗靶点。
