miR-135b-3p调控XAF1表达影响甲状腺癌细胞的迁移、侵袭和放射增敏性

基础医学与临床 ›› 2020, Vol. 40 ›› Issue (6): 790-796.

miR-135b-3p调控XAF1表达影响甲状腺癌细胞的迁移、侵袭和放射增敏性

曹邓晗¹, 陈奎生^2*

1.郑州市第一人民医院内分泌科, 河南郑州 450004;
2.郑州大学第一附属医院病理科, 河南郑州 450052

收稿日期:2019-06-10 修回日期:2019-11-04 出版日期:2020-06-05 发布日期:2020-05-29
通讯作者: *qum4483@163.com
基金资助:
河南省医学科技攻关计划(201503221)

miR-135b-3p regulates XAF1 expression and affects migration, invasion and radio sensitization of thyroid cancer cells

CAO Deng-han¹, CHEN Kui-sheng^2*

1. Department of Endocrinology, Zhengzhou First People’s Hospital, Zhengzhou 450004;
2. Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

Received:2019-06-10 Revised:2019-11-04 Online:2020-06-05 Published:2020-05-29
Contact: *qum4483@163.com

摘要/Abstract

摘要： 目的探讨miR-135b-3p对甲状腺癌细胞迁移、侵袭和放射敏感性的影响以及其可能的调控机制。方法培养正常甲状腺细胞Nthy-ori 3-1、甲状腺癌细胞K1和TPC-1,RT-qPCR检测细胞中miR-135b-3p表达,Western blot检测细胞中X染色体连锁凋亡抑制蛋白相关因子1(XAF1)表达。转染anti-miR-135b-3p至TPC-1细胞抑制miR-135b-3p表达,Transwell、Western blot及克隆形成实验分别检测抑制miR-135b-3p表达对TPC-1细胞迁移和侵袭、E-cadherin和MMP-2蛋白表达及对TPC-1细胞放射敏感性的影响。双荧光素酶报告基因实验验证miR-135b-3p与XAF1之间的靶向调控关系。结果与Nthy-ori 3-1细胞相比,K1和TPC-1细胞中miR-135b-3p表达水平显著升高(P＜0.05),XAF1蛋白表达水平显著降低(P＜0.05)。抑制miR-135b-3p表达可抑制TPC-1细胞的迁移和侵袭能力(P＜0.05),促进TPC-1细胞E-cadherin蛋白表达(P＜0.05),抑制MMP-2蛋白表达(P＜0.05),增强TPC-1细胞的放射敏感性(P＜0.05)。miR-135b-3p靶向负调控XAF1表达。抑制XAF1表达可降低抑制miR-135b-3p表达对TPC-1细胞迁移、侵袭及放射敏感性的影响。结论 miR-135b-3p通过下调XAF1表达促进甲状腺癌细胞的迁移和侵袭能力,并降低其放射增敏性,是甲状腺癌的潜在治疗靶点。

关键词: 甲状腺癌, miR-135b-3p, XAF1, 迁移, 放射增敏

Abstract: Objective To investigate the effects of miR-135b-3p on migration, invasion and radio sensitivity of thyroid cancer cells and its possible regulatory mechanisms. Methods Normal thyroid cells Nthy-ori 3-1, thyroid cancer cells K1 and TPC-1 were cultured. The expression of miR-135b-3p was detected by RT-qPCR. The expression of XAF1 protein was detected by Western blot. Anti-miR-135b-3p was transfected to TPC-1 cells to inhibit the expression of miR-135b-3p. Transwell, Western blot and cloning formation assay were used to detect the effect of inhibition of miR-135b-3p expression on migration and invasion of TPC-1 cells, and the expression of E-cadherin and MMP-2 protein and radio sensitivity, respectively. The dual luciferase reporter gene assay verified the targeted regulatory relationship between miR-135b-3p and XAF1. Results Compared with Nthy-ori 3-1 cells, the expression of miR-135b-3p was significantly increased in K1 and TPC-1 cells (P＜0.05), and the expression of XAF1 protein was significantly decreased (P＜0.05). Inhibition of miR-135b-3p expression could inhibit the migration and invasion of TPC-1 cells (P＜0.05), promote the expression of E-cadherin protein in TPC-1 cells (P＜0.05), inhibit the expression of MMP-2 protein (P＜0.05), and enhance the radio sensitivity of TPC-1 cells (P＜0.05). miR-135b-3p targeted negative regulation of XAF1 expression. Inhibition of XAF1 expression partially reduced the effect of inhibiting miR-135b-3p expression on TPC-1 cell migration and invasion as well as the enhanced radio sensitivity. Conclusions R-135b-3p promotes the migration and invasion of thyroid cancer cells by down-regulating the expression of XAF1, and reduces its radio sensitization. It is a potential therapeutic target for thyroid cancer.

Key words: thyroid cancer, miR-135b-3p, XAF1, migration, radio sensitization

中图分类号:

R736.1

曹邓晗, 陈奎生. miR-135b-3p调控XAF1表达影响甲状腺癌细胞的迁移、侵袭和放射增敏性[J]. 基础医学与临床, 2020, 40(6): 790-796.

CAO Deng-han, CHEN Kui-sheng. miR-135b-3p regulates XAF1 expression and affects migration, invasion and radio sensitization of thyroid cancer cells[J]. Basic & Clinical Medicine, 2020, 40(6): 790-796.

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