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微小RNA-140-3p通过抑制肺腺癌细胞中的Wnt/β-连环蛋白信号通路增强顺铂敏感性并减弱干细胞样特性。

miR-140-3p enhances cisplatin sensitivity and attenuates stem cell-like properties through repressing Wnt/β-catenin signaling in lung adenocarcinoma cells.

作者信息

Wu Shuoming, Wang Haoran, Pan Yinpeng, Yang Xiangbao, Wu Duoguang

机构信息

Department of Thoracic Surgery, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu 222000, P.R. China.

Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.

出版信息

Exp Ther Med. 2020 Aug;20(2):1664-1674. doi: 10.3892/etm.2020.8847. Epub 2020 Jun 5.

Abstract

Lung adenocarcinoma (LUAD) is the most predominant subtype of non-small cell lung cancer (NSCLC) that is experiencing the fastest growth rate in incidence. Chemoresistance and the presence of cancer stem cells are considered to be the main obstacles preventing the successful treatment of patients with NSCLC, the molecular mechanism of which remains poorly understood. The present study aimed to investigate the effects of microRNA (miR)-140-3p on cisplatin sensitivity and stem cell-like properties of LUAD cells. Analysis of publicly available data demonstrated that miR-140-3p expression was downregulated in LUAD, and positively associated with the overall survival rate of patients. In addition, transfection with the miR-140-3p mimic reduced LUAD cell viability and induced apoptosis following treatment with cisplatin whilst decreasing stem cell-like properties. miR-140-3p overexpression was also found to attenuate cisplatin resistance and reduce stem cell-like properties in LUAD cells by suppressing Wnt/β-catenin signaling, all of which were reversed by the overexpression of β-catenin. Taken together, results of the present study suggest miR-140-3p to be an effective therapeutic strategy for patients with LUAD.

摘要

肺腺癌(LUAD)是非小细胞肺癌(NSCLC)中最主要的亚型,其发病率增长速度最快。化疗耐药性和癌症干细胞的存在被认为是阻碍NSCLC患者成功治疗的主要障碍,其分子机制仍知之甚少。本研究旨在探讨微小RNA(miR)-140-3p对LUAD细胞顺铂敏感性和干细胞样特性的影响。对公开可用数据的分析表明,LUAD中miR-140-3p表达下调,且与患者的总生存率呈正相关。此外,用miR-140-3p模拟物转染可降低LUAD细胞活力,并在顺铂处理后诱导细胞凋亡,同时降低干细胞样特性。还发现miR-140-3p过表达通过抑制Wnt/β-连环蛋白信号通路减弱LUAD细胞的顺铂耐药性并降低干细胞样特性,而β-连环蛋白的过表达可逆转所有这些作用。综上所述,本研究结果表明miR-140-3p是LUAD患者的一种有效治疗策略。

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