MicroRNA-138 inhibits migration and invasion of non-small cell lung cancer cells by targeting LIMK1 (Retracted article. See vol. 24, 2021)
MicroRNA-138 inhibits migration and invasion of non-small cell lung cancer cells by targeting LIMK1 (Retracted article. See vol. 24, 2021)
复制标题
MicroRNA-138通过靶向LIMK1抑制非小细胞肺癌细胞的迁移和侵袭
DOI：
10.3892/mmr.2016.5769
复制
发表时间：
2016-11-01
影响因子：
3.4
通讯作者：
Zhou, Hui
中科院分区：
文献类型：
--
作者：
Tan, Yanjuan;Hu, Huaidong;Zhou, Hui
此前已证明，microRNA(MiR)-138在多种类型的人类癌症中具有抑制作用，包括非小细胞肺癌(NSCLC)。LIM结构域蛋白1(LIM domain kinase1，LIMK1)是一种丝氨酸/苏氨酸激酶，通过Cofilin的磷酸化和失活来调节肌动蛋白聚合。以往的研究已报道LIMK1与非小细胞肺癌相关；然而，LIMK1的潜在调控机制以及LIMK1与非小细胞肺癌细胞中miR-138之间的关联在很大程度上仍不清楚。本研究旨在揭示miR-138和LIMK1在NSCLC细胞迁移和侵袭中的调控作用。逆转录-定量聚合酶链式反应和蛋白印迹分析检测基因和蛋白的表达水平。用Transwell和伤口愈合试验来确定细胞的侵袭和迁移。荧光素酶报告实验用于确定miR-138和LIMK1之间的靶向关联。本研究表明，miR-138在NSCLC组织和细胞系中的表达显著下调，而LIMK1的表达水平显著上调。在NSCLC H460细胞中进一步鉴定LIMK1是miR-138的直接靶点。此外，miR-138的过表达显著抑制了H460细胞中LIMK1的蛋白表达，而miR-138的下调则上调了LIMK1的蛋白表达。此外，miR-138过表达显著抑制NSCLC细胞的迁移和侵袭，而LIMK1过表达则显著促进NSCLC细胞的迁移和侵袭。对其潜在分子机制的研究表明，miR-138的过表达显著降低了cofilin信号的活性，而miR-138的敲除显著增强了cofilin信号的活性。综上所述，本研究提示miR-138可能通过靶向LIMK1/cofilin信号通路抑制NSCLC细胞的迁移和侵袭。因此，miR-138/LIMK1/cofilin可能被认为是治疗非小细胞肺癌的潜在靶点。
MicroRNA (miR)-138 has previously been demonstrated to have a suppressive role in numerous types of human cancer, including non-small cell lung cancer (NSCLC). LIM domain kinase 1 (LIMK1) is a serine/threonine kinase that regulates actin polymerization via phosphorylation and inactivation of cofilin. Previous studies have reported that LIMK1 is associated with NSCLC; however, the underlying regulatory mechanism of LIMK1, and the association between LIMK1 and miR-138 in NSCLC cells, remains largely unknown. The present study aimed to reveal the regulatory roles of miR-138 and LIMK1 in NSCLC cell migration and invasion. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to examine the mRNA and protein expression levels. Transwell and wound healing assays were conducted to determine cell invasion and migration. A luciferase reporter assay was used to determine the target association between miR-138 and LIMK1. The present study demonstrated that miR-138 was markedly downregulated in NSCLC tissues and cell lines, whereas the expression levels of LIMK1 were significantly upregulated. LIMK1 was further identified as a direct target of miR-138 in NSCLC H460 cells. Furthermore, overexpression of miR-138 significantly inhibited the protein expression of LIMK1, whereas knockdown of miR-138 upregulated the protein expression of LIMK1 in H460 cells. In addition, overexpression of miR-138 significantly inhibited the migration and invasion of NSCLC cells; however, overexpression of LIMK1 significantly promoted NSCLC cell migration and invasion. An investigation into the underlying molecular mechanism revealed that overexpression of miR-138 significantly decreased cofilin signaling activity, whereas knockdown of miR-138 notably enhanced cofilin signaling activity. In conclusion, the present study suggests that miR-138 may inhibit the migration and invasion of NSCLC cells by targeting the LIMK1/cofilin signaling pathway. Therefore, miR-138/LIMK1/cofilin may be considered a potential therapeutic target for the treatment of NSCLC.