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

• 研究论文 • 上一篇    下一篇

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2   

  1. 1. 襄阳市中医院
    2. 武汉市中医医院
  • 收稿日期:2020-04-10 修回日期:2020-06-24 出版日期:2021-03-05 发布日期:2021-03-01
  • 通讯作者: 刘亚琪 E-mail:420278921ly@sina.com

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

  • Received:2020-04-10 Revised:2020-06-24 Online:2021-03-05 Published:2021-03-01
  • Contact: 刘亚琪 E-mail:420278921ly@sina.com

摘要: 目的 探讨miR-205是否可以调控无翼样MMTV结合点家族蛋白5a (Wnt-5a) 抑制甲状腺乳头状癌(PTC)细胞增殖。方法 用RT-qPCR检测60例PTC组织标本和相邻正常组织中的miR-205和Wnt-5a的表达,miR-205和Wnt5a之间进行进一步相关性分析。并探讨miR-205低表达是否与PTC 肿瘤范围-淋巴结转移-远处转移(TMN)分期、淋巴结转移等相关。同时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。此外,过表达和抑制miR-205后通过CCK-8法检测PTC细胞增殖。通过异种移植物肿瘤形成试验观察抑制miR-205是否加速PTC 的肿瘤生长。使用在线目标基因预测软件和双重荧光素酶报告基因试验分别预测和验证Wnt-5a是否为miR-205的靶基因。结果 在PTC组织中miR-205的表达显著低于周围正常组织 (P<0.05),而Wnt5a mRNA表达显著高于周围正常组织(P<0.05)。PTC患者TNM分期以及淋巴结转移严重程度在miR-205低表达患者显著高于高表达患者(P<0.05)。低表达miR-205的甲状腺乳头状癌患者的预后较差。正常甲状腺滤泡上皮细胞系NTHY-OR-3-1中miR-205表达显著低于PTC细胞系K1以及BCPAP (P<0.05)。发现 miR-205 过表达在体外抑制了 PTC 细胞增殖 (P<0.05)。miR-205过表达并抑制了 裸鼠PTC 肿瘤生长。荧光素酶试验证实Wnt5a 是miR-205的靶点基因。结论 miR-205在PTC中发挥抗癌作用,这可能为PTC的提供新的治疗靶点。

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 accelerate 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 Wnt5a 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 has 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 Wnt5a was the target gene of miR-205 by luciferase reporter assay. Conclusions miR-205 plays an anti-cancer role in PTC, which may provide a new therapeutic target for PTC.