Published online Jun 7, 2014. doi: 10.3748/wjg.v20.i21.6515
Revised: March 4, 2014
Accepted: April 30, 2014
Published online: June 7, 2014
AIM: To investigate the biological role and underlying mechanism of miR-132 in colorectal cancer (CRC) progression and invasion.
METHODS: Quantitative RT-PCR analysis was used to examine the expression levels of miR-132 in five CRC cell lines (SW480, SW620, HCT116, HT29 and LoVo) and a normal colonic cell line NCM460, as well as in tumor tissues with or without metastases. The Kaplan-Meier method was used to analyze the prognostic significance of miR-132 in CRC patients. The biological effects of miR-132 were assessed in CRC cell lines using the transwell assay. Quantitative RT-PCR and western blot analyses were employed to evaluate the expression of miR-132 targets. The regulation of ZEB2 by miR-132 was confirmed using the luciferase activity assay.
RESULTS: miR-132 was significantly down-regulated in the CRC cell lines compared with the normal colonic cell line (P < 0.05), as well as in the CRC tissues with distant metastases compared with the tissues without metastases (10.52 ± 4.69 vs 23.11 ± 7.84) (P < 0.001). Down-regulation of miR-132 was associated with tumor size (P = 0.016), distant metastasis (P = 0.002), and TNM stage (P = 0.020) in CRC patients. Kaplan-Meier survival curve analysis indicated that patients with low expression of miR-132 tended to have worse disease-free survival than patients with high expression of miR-132 (P < 0.001). Moreover, ectopic expression of miR-132 markedly inhibited cell invasion (P < 0.05) and the epithelial-mesenchymal transition (EMT) in CRC cell lines. Further investigation revealed ZEB2, an EMT regulator, was a downstream target of miR-132.
CONCLUSION: Our study indicated that miR-132 plays an important role in the invasion and metastasis of CRC.
Core tip: In this study, we reported the clinical significance and biological effects of miR-132 in colorectal cancer (CRC). We found that miR-132 was significantly down-regulated in tumor cell lines and CRC tissues with distant metastases. Down-regulation of miR-132 was associated with aggressive tumor phenotypes and adverse prognosis in CRC patients. Moreover, we showed that ectopic expression of miR-132 significantly inhibited cell invasion and the epithelial-mesenchymal transition (EMT), whereas knockdown of miR-132 promoted cell invasion and EMT in CRC cells. Further investigation revealed ZEB2, an EMT regulator, was a downstream target of miR-132.