miR-205通过靶向调控Wnt-5a抑制乳头状甲状腺癌的细胞增殖

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (3): 358-363.

miR-205通过靶向调控Wnt-5a抑制乳头状甲状腺癌的细胞增殖

刘亚琪¹, 郑承红^1,2*

1.湖北中医药大学, 湖北武汉 430065;
2.武汉市中医医院内分泌科, 湖北武汉 430000

收稿日期:2020-04-10 修回日期:2020-06-27 出版日期:2021-03-05 发布日期:2021-03-01
通讯作者: ^*dasboat77@163.com
基金资助:
湖北省自然科学基金[2017(20)]

miR-205 inhibits cell proliferation of papillary thyroid carcinoma by regulating Wnt-5a

LIU Ya-qi¹, ZHENG Cheng-hong^1,3*

1. Hubei University of Chinese Medicine, Wuhan 430065;
2. Department of Endocrinology, Wuhan Hospital of Traditional Chinese Medicine, Wuhan 430000,China

Received:2020-04-10 Revised:2020-06-27 Online:2021-03-05 Published:2021-03-01
Contact: ^*dasboat77@163.com

摘要/Abstract

摘要： 目的探讨miR-205是否能通过靶向调控无翼样MMTV结合点家族蛋白5a(Wnt-5a)而抑制乳头状甲状腺癌(PTC)的细胞增殖。方法用RT-qPCR检测60例PTC组织、癌旁组织标本中miR-205和Wnt-5a的表达,并对miR-205和Wnt-5a之间进行相关性分析;探讨miR-205低表达是否与PTC 的TMN分期、淋巴结转移等相关;用RT-qPCR检测人正常甲状腺滤泡上皮细胞系NTHY-OR-3-1和PTC细胞系(K1和BCPAP)中miR-205的表达水平;通过CCK-8法检测过表达或抑制miR-205后对PTC细胞增殖的影响;通过异种移植物肿瘤形成实验观察抑制miR-205是否能加速PTC的生长;采用在线目标基因预测软件和双荧光素酶报告基因实验预测和验证Wnt-5a是否为miR-205的靶基因。结果 PTC组织中miR-205的表达水平显著低于癌旁组织,而Wnt-5a mRNA含量显著高于癌旁组织(P＜0.05);PTC患者TNM分期以及淋巴结转移严重程度与miR-205表达呈负相关(P＜0.05),低表达miR-205的PTC患者预后较差;NTHY-OR-3-1细胞中的miR-205表达水平明显高于在K1和BCPAP细胞中的水平;体外实验表明过表达miR-205抑制PTC 的细胞增殖(P＜0.05);miR-205过表达抑制裸鼠 PTC的肿瘤生长;荧光素酶报告基因实验证实Wnt-5a是miR-205的靶点基因。结论 miR-205在PTC中发挥抑癌作用,其靶向调控Wnt-5a的功能可为PTC的治疗提供新的靶点。

关键词: 乳头状甲状腺癌, miR-205, 细胞增殖, Wnt-5a

Abstract: Objective To investigate whether miR-205 can regulate wingless-type MMTV integration site family member 5a (Wnt-5a) to inhibit the papillary thyroid carcinoma (PTC) cell proliferation. Methods RT-qPCR was used to detect the expression of miR-205 and Wnt-5a in PTC tissues and adjacent normal tissues.Further correlation analysis between miR-205 and Wnt-5a was carried out. The low expression of miR-205 related to the stage of PTC TMN and lymph node metastasis was also discussed. Meanwhile, RT-qPCR was also used to detect NTHY-OR-3-1 and PTC cell lines (K1 and BCPAP). In addition, the proliferation of PTC cells was detected by CCK-8 after over expression and inhibition of miR-205. Xenograft tumor formation test was used to observe whether inhibition of miR-205 acceler- ates the growth of tumor. The online target gene prediction software and dual luciferase reporter gene test were used to predict and verify whether Wnt-5a is the target gene of miR-205. Results The expression of miR-205 was significantly lower than that of surrounding normal tissues, and the expression of Wnt-5a was significantly higher. TNM stage and lymph node metastasis severity of PTC patients were significantly higher in patients with low miR-205 expression than in patients with high miR-205 expression. Low expression of miR-205 showed a poor survival rate. Expression of miR-205 in NTHY-OR-3-1 was significantly lower than that of K1 and BCPAP. miR-205 inhibited the proliferation of PTC cells. Over-expression of miR-205 also inhibited the growth of PTC. It was confirmed that Wnt-5a was the target gene of miR-205 by luciferase reporter assay. Conclusions miR-205 plays an anti-cancer role in PTC, which may be a potential therapeutic target.

Key words: papillary thyroid carcinoma, miR-205, cell proliferation, Wnt-5a

中图分类号:

R73-3

刘亚琪, 郑承红. miR-205通过靶向调控Wnt-5a抑制乳头状甲状腺癌的细胞增殖[J]. 基础医学与临床, 2021, 41(3): 358-363.

LIU Ya-qi, ZHENG Cheng-hong. miR-205 inhibits cell proliferation of papillary thyroid carcinoma by regulating Wnt-5a[J]. Basic & Clinical Medicine, 2021, 41(3): 358-363.

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