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

Abstract

BackgroundNon-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.MethodsQuantitative 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.ResultsMiR-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.ConclusionsMiR-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.

Multidimensional Roles of Collagen Triple Helix Repeat Containing 1 (CTHRC1) in Malignant Cancers

“…Two independent analyses using lung cancer specimens revealed that overexpression of CTHRC1 strikingly associated with differentiation degree, clinical stage, T classification, lymph node metastasis, distant metastasis and cigarette smoke as well as with poor clinical survival time of the patients compared with patient with low CTHRC1 expression 11, 21. Furthermore, the observed results displayed that there were no significant differences between CTHRC1 and mRNA levels with different genders, ages or pathological types 22. Particularly, an ongoing study revealed that CTHRC1 interacted with microRNA-30b to decrease the ability of invasion and migration in NSCLC patients 22.…”

“…Furthermore, the observed results displayed that there were no significant differences between CTHRC1 and mRNA levels with different genders, ages or pathological types 22. Particularly, an ongoing study revealed that CTHRC1 interacted with microRNA-30b to decrease the ability of invasion and migration in NSCLC patients 22. These results suggest that CTHRC1 overexpression is a valuable prognosis biomarker for NSCLC.…”

“…Recent research has explored the aberrant up-regulation of CTHRC1 in NSCLC 11, 21, 22, Ke al el showed that overexpression of CTHRC1 increased NSCLC proliferation, invasion and metastasis in vitro via the Wnt/β-catenin signaling pathway 11. Based on this observation, paraffin-embedded immunohistochemical analysis of CTHRC1 in NSCLC patient tissues (212/292, 72.60%) illustrated that the up-regulated levels of both mRNA and protein were evidently higher than those in the paired adjacent non-cancerous tissues (6/66, 9.09%) (p<0.001).…”

The role of microRNA in metastatic processes of non-small cell lung carcinoma

“…in vitro examinations revealed that mir-30b inhibits cell invasion and migration through targeting and downregulating cthrc1 of a549 and calu-3 cells. Not only was the expression of cthrc1 decreased, mmp-2 and mmp-9 expression was also reduced while Timp-1 expression was increased in mir-30b mimic transfected a549 and calu-3 cells 138 . Timp1 regulates extracellular matrix catabolism but the major effect in tumour tissue is promotion of cell growth and anti-apoptotic activity 139 .…”

“…chen et al evaluated the expression of mir-30b in Nsclc (ref. 138 ). The median ± sd expression levels of mir-30b were associated with lymph node metastasis as follows: Nsclc patients lNm+ had 0.2147 ± 0.0670 levels; Nsclc patients lNm-had 0.3129 ± 0.1234 levels.…”