MicroRNA-138 inhibits migration and invasion of non-small cell lung cancer cells by targeting LIMK1.

نویسندگان

  • Yanjuan Tan
  • Huaidong Hu
  • Wuyuan Tan
  • Longyu Jin
  • Jianxin Liu
  • Hui Zhou
چکیده

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.

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عنوان ژورنال:
  • Molecular medicine reports

دوره 14 5  شماره 

صفحات  -

تاریخ انتشار 2016