microRNA-30b inhibits cell invasion and migration through targeting collagen triple helix repeat containing 1 in non-small cell lung cancer

摘要

Background Non-small cell lung cancer (NSCLC) is the largest histological subgroup of lung cancer and has increased in prevalence in China over the past 5?years. The 5-year survival rate has remained at 15–20?%, with a median survival of 8–12?months. The tumorigenesis and progression of NSCLC is orchestrated by numerous oncogene and anti-oncogene mutations and insights into microRNA function have increased our understanding of the process. Here, we investigated the effects of miR-30b on NSCLC cell invasion and migration and explored the underlying molecular mechanisms involved. Methods Quantitative reverse transcription PCR, wound healing assay, trans-well assays, western blotting and dual luciferase assays were performed to investigate the molecular mechanisms of miR-30b in NSCLC cells. Results MiR-30b was down-regulated and Cthrc1 up-regulated in NSCLC tissues. Both were associated with tumor differentiation, TNM stage and lymph node metastases. Up-regulation of miR-30b restricted A549 and Calu-3 cell invasion and migration. Additionally, the expression of Cthrc1, matrix metalloproteinase-9 and matrix metalloproteinase-2 was reduced, while metallopeptidase inhibitor-1 expression increased. Bioinformatics analysis identified Cthrc1 as a target of miR-30b and western blotting and luciferase reporter assays confirmed that miR-30b regulates Cthrc1 by directly binding to its 3′UTR. Transfection of Cthrc1 without the 3′UTR restored the miR-30b inhibiting cell invasion. Up-regulation of miR-30b or down-regulation of Cthrc1 had potential significance in the invasion and metastasis of NSCLC. Conclusions MiR-30b was down-regulated and Cthrc1 up-regulated in NSCLC tissues. Both of them were related to tumor differentiation, TNM stage and lymph node metastases. MiR-30b affected NSCLC cells invasion and migration by regulating Cthrc1.