Downregulation of miR-518a-3p activates the NIK-dependent NF-κB pathway in colorectal cancer

The aim of the present study was to investigate the biological role and underlying mechanisms of action of miR-518a-3p in the progression and invasion of colorectal cancer (CRC). Reverse transcription-quantitative PCR (RT-qPCR) was used to examine the mRNA expression levels of miR-518a-3p in 5 CRC cell lines (SW480, SW620, HCT116, HT29 and LoVo) in a normal colonic cell line, NCM460, as well as in tumor tissues with or without metastases. The biological effects of miR-518a-3p were assessed in the CRC cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis, and RT-qPCR and western blot analyses were employed to evaluate the expression of miR-518a-3p targets. The regulation of NF-kappa B-inducing kinase (NIK) by miR-518a-3p was confirmed using luciferase activity assays. Our results revealed that miR-518a-3p was significantly downregulated 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. The downregulation of miR-518a-3p was associated with tumor size, distant metastasis and TNM stage in the patients with CRC. Moreover, the ectopic expression of miR-518a-3p and the inhibition of NIK by RNA interference markedly reduced cell proliferation and enhanced the apoptosis of CRC cells. Further experiments revealed that NIK, a regulator of NF-kappa B, was a downstream target of miR-518a-3p. The presents findings indicate that miR-518a-3p plays an important role in the progression of CRC by targeting NIK.