LncRNA TUG1通过miR-145/KIAA1199轴对结直肠癌细胞转移和上皮间质转化的影响

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摘要目的探讨长链非编码RNA TUG1（LncRNA TUG1）通过微RNA-145（miR-145）/KIAA1199轴对结直肠癌细胞转移和上皮间质转化（EMT）的影响。方法收集浙江省嘉兴市第一医院2020年8月至2021年2月经病理诊断证实的、术前未接受放化疗的30例结直肠癌患者癌组织及癌旁组织标本。RT-qPCR检测LncRNA TUG1、miR-145和KIAA1199在Colo320、HCT116、NCM460细胞及癌和癌旁组织中的差异表达；分析LncRNA TUG1和miR-145的作用靶点及相关性；检测LncRNA TUG1通过miR-145对Colo320细胞发展和KIAA1199表达的影响；分析TUG1、KIAA1199下调对Colo320细胞增殖、侵袭及EMT的影响。结果癌组织LncRNA TUG1、KIAA1199表达高于癌旁组织，miR-145表达低于癌旁组织（P < 0.01）。HCT116、Colo320细胞中LncRNA TUG1和KIAA1199表达高于NCM460细胞，miR-145表达低于NCM460细胞（P < 0.01）。TUG1下调组细胞活力（24、48、72 h），细胞侵袭数目低于下调对照组（P < 0.05）；TUG1下调组N-cadherin、Vimentin和Snail表达低于下调对照组，E-cadherin表达高于下调对照组（P < 0.01）。LncRNA TUG1野生型+miR-145模拟物组荧光素酶活性低于LncRNA TUG1野生型+模拟物对照组（P < 0.01）；LncRNA TUG1突变型+模拟物对照组与LncRNA TUG1突变型+miR-145模拟物组荧光素酶活性比较，差异无统计学意义（P > 0.05）。TUG1过表达+miR-145模拟物组细胞侵袭数目，细胞活力（24、48、72 h）高于过表达对照+miR-145模拟物组（P < 0.05）；TUG1过表达+miR-145模拟物组N-cadherin、Vimentin、Snail表达高于过表达对照+miR-145模拟物组，E-cadherin表达低于过表达对照+miR-145模拟物组（P < 0.01）。KIAA1199下调组细胞活力（24、48、72 h），侵袭数目低于下调对照组（P < 0.05）；KIAA1199下调组N-cadherin、Vimentin、Snail表达低于下调对照组，E-cadherin表达高于下调对照组（P < 0.01）。结论 LncRNA TUG1通过miR-145促进KIAA1199表达，加速Colo320细胞增殖、侵袭及EMT。

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	李海强李彦沈徐宁蒋红钢

关键词 ：长链非编码RNA TUG1, 微RNA-145, KIAA1199, 结直肠癌

Abstract：Objective To investigate the effect of LncRNA TUG1 on colorectal cancer cell metastasis and epithelial mesenchymal transformation (EMT) through microRNA-145 (miR-145)/KIAA1199 axis. Methods A total of 30 patients with colorectal cancer who were pathologically confirmed and did not receive preoperative chemoradiotherapy were collected from the First Hospital of Jiaxing, Zhejiang Province from August 2020 to February 2021. Differential expressions of lncRNA TUG1, miR-145, and KIAA1199 in Colo320, HCT116, and NCM460 cells, cancer and paracancerous tissues were detected by RT-qPCR; the effect target and correlation of LncRNA TUG1 and miR-145 were analyzed; the effects of lncRNA TUG1 on Colo320 cell development and KIAA1199 expression via miR-145 were detected; the effects of TUG1 or KIAA1199 down-regulation on Colo320 cell proliferation, invasion, and EMT were detected. Results The expression levels of lncRNA TUG1 and KIAA1199 in cancer tissues were higher than those in paracancerous tissues, and the expression level of miR-145 was lower than that in paracancerous tissues (P < 0.01). The expression levels of LncRNA TUG1 and KIAA1199 in HCT116 and Colo320 cells were higher than those in NCM460 cell, and the expression level of miR-145 was lower than that in NCM460 cell (P < 0.01). The cell viability (24, 48, 72 h) and invasion number of TUG1 down-regulated group were lower than those of down-regulated control group (P < 0.05); the expression levels of N-cadherin, Vimentin, and Snail in TUG1 down-regulated group were lower than those in down-regulated control group, while the expression of E-cadherin was higher than that in down-regulated control group (P < 0.01). The lucifase activity of LncRNA TUG1 wildtype+miR-145 mimics group was lower than that of LncRNA TUG1 wildtype+ mimics control group (P < 0.01); there was no significant difference in lucifase activity between LncRNA TUG1 mutant+ mimic group and LncRNA TUG1 mutant+miR-145 mimic group (P > 0.05). The number of cell invasion and cell viability (24, 48, 72 h) in TUG1 overexpression+miR-145 mimics group were higher than those in overexpression control+miR-145 mimics group (P < 0.05); the expression levels of N-cadherin, Vimentin, and Snail in TUG1 overexpression+miR-145 mimics group were higher than those in overexpression control+miR-145 mimics group, while the expression level of E-cadherin was lower than that in overexpression control+miR-145 mimics group (P < 0.01). The cell viability (24, 48, 72 h) and invasion number of KIAA1199 down-regulated group were lower than those of down-regulated control group (P < 0.05); the expression levels of N-cadherin, Vimentin, and Snail in KIAA1199 down-regulated group were lower than those in down-regulated control group, while the expression level of E-cadherin was higher than that in down-regulated control group (P < 0.01). Conclusion LncRNA TUG1 promotes KIAA1199 expression through miR-145 and accelerates the proliferation, invasion, and EMT of Colo320 cell.

Key words： Long non-coding TUG1 microRNA-145 KIAA1199 Colorectal cancer

基金资助:国家自然科学基金资助项目（82002982）。

通讯作者: 蒋红钢（1965.5-），男，主任医师；研究方向：胃肠肿瘤、肛肠疾病。

作者简介: 李海强（1978.11-），男，副主任医师；研究方向：胃肠外科、胃肠肿瘤、肛肠疾病。

引用本文:

李海强李彦沈徐宁蒋红钢. LncRNA TUG1通过miR-145/KIAA1199轴对结直肠癌细胞转移和上皮间质转化的影响[J]. 中国医药导报, 2021, 18(36): 8-13.
LI Haiqiang LI Yan SHEN Xuning JIANG Honggang. Effect of lncRNA TUG1 on colorectal cancer cell metastasis and epithelial mesenchymal transformation through miR-145/KIAA1199 axis#br#. 中国医药导报, 2021, 18(36): 8-13.

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