title: Downregulation of miR-518a-3p activates the NIK-dependent NF-κB pathway in colorectal cancer.
abstract: 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-κB-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-κB, 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.
authors: Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: L L
authors: LL
authors: Qu
authors: Department of Gastroenterology Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: L
authors: L
authors: He
authors: Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: X
authors: X
authors: Zhao
authors: Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: W
authors: W
authors: Xu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000097782:NF-kappaB-Inducing Kinase; C571457:MIRN518 microRNA, human