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miR-142-5p 通过靶向 Yin Yang 1 抑制上皮-间质转化调控肺癌细胞转移。

MiR-142-5p Suppresses Lung Cancer Cell Metastasis by Targeting Yin Yang 1 to Regulate Epithelial-Mesenchymal Transition.

机构信息

Department of Thoracic Oncology, the Third Affiliated Hospital of Xinjiang Medical University, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, China.

Department of Tumor Radiotherapy, Ili Kazakh Autonomous Prefecture State Friendship Hospital, Yining, China.

出版信息

Cell Reprogram. 2020 Dec;22(6):328-336. doi: 10.1089/cell.2020.0023.

Abstract

This study aimed to investigate the mechanism of miR-142-5p and Yin Yang 1 (YY1) on regulating epithelial-mesenchymal transition (EMT) in lung cancer cell metastasis. The expressions of YY1 and miR-142-5p in different lung cancer cell lines were negatively correlated. The results of the dual-luciferase reporter assay further validated that miR-142-5p directly targeted YY1. Subsequently, transwell assays, wound-healing assay, and transplantation tumor model in nude mice proved that YY1 could promote the metastasis of lung cancer cells, whereas miR-142-5p impaired the stimulating effect of YY1 on the metastasis ability of lung cancer cells and . Western blot and quantitative real-time polymerase chain reaction analysis of the EMT-related proteins indicated that YY1 could enhance the metastasis ability of lung cancer cells by promoting EMT. On the contrary, miR-142-5p constrained the expression of mesenchymal markers by targeting YY1, reversed the differentiation of cells into mesenchymal cells, and weakened the metastasis ability of tumor cells and . In summary, miR-142-5p may regulate the expressions of EMT-related proteins by targeting YY1, thereby inhibiting lung cancer metastasis, which provides a promising therapeutic target for lung cancer.

摘要

本研究旨在探讨 miR-142-5p 和 Yin Yang 1(YY1)调节肺癌细胞转移上皮-间充质转化(EMT)的机制。不同肺癌细胞系中 YY1 和 miR-142-5p 的表达呈负相关。双荧光素酶报告基因检测进一步验证了 miR-142-5p 可直接靶向 YY1。随后,Transwell 检测、划痕愈合检测和裸鼠移植瘤模型证实,YY1 可促进肺癌细胞的转移,而 miR-142-5p 则削弱了 YY1 对肺癌细胞转移能力的刺激作用。Western blot 和定量实时聚合酶链反应分析 EMT 相关蛋白表明,YY1 可通过促进 EMT 增强肺癌细胞的转移能力。相反,miR-142-5p 通过靶向 YY1 抑制间充质标志物的表达,逆转细胞向间充质细胞的分化,从而削弱肿瘤细胞的转移能力。综上所述,miR-142-5p 可能通过靶向 YY1 调节 EMT 相关蛋白的表达,从而抑制肺癌转移,为肺癌治疗提供了有前途的靶点。

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