title: MicroRNA-370 inhibits the progression of non-small cell lung cancer by downregulating oncogene TRAF4.
abstract: Lung cancer is the leading cause of cancer-related deaths, of which most can be attributed to non-small cell lung cancer (NSCLC). microRNAs (miRNAs) are a group of small non-coding RNAs that focus on post-transcriptional modification. The present study aimed to investigate the role and function of microRNA-370 (miR-370) in NSCLC and explore the underlying functional mechanisms. We found that miR-370 was significantly downregulated in the tumor tissues of NSCLC patients as well as in NSCLC cell lines. Overexpression of miR-370 by infection of recombinant lentivirus markedly inhibited cell proliferation and promoted cell apoptosis of NSCLC cells. In addition, in vivo tumor formation of NSCLC cells was decreased by miR-370 overexpression. Through bioinformatic analysis, we found that tumor necrosis factor receptor-associated factor 4 (TRAF4), an oncogene as previously reported, was predicted as a putative target gene of miR-370. The direct targeting relationship between miR-370 and the 3'-untranslated region was validated by dual-luciferase reporter assay. Furthermore, overexpression of miR-370 downregulated the protein expression of TRAF4 in the NSCLC cells. Moreover, the growth inhibitory effect of miR-370 overexpression on NSCLC cells was abrogated by TRAF4 overexpression. In conclusion, our results suggest that miR-370 plays an important role in NSCLC by regulating TRAF4 and may be a potential target for the treatment of NSCLC.
authors.affiliation: Respiratory Department, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
authors.forename: Tianjun
authors.initials: T
authors.lastname: Chen
authors.affiliation: Ultrasound Department, Hua-shan Central Hospital of Xi'an, Xi'an, Shaanxi, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Respiratory Department, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
authors.forename: Sifang
authors.initials: S
authors.lastname: Feng
authors.affiliation: Respiratory Department, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.affiliation: Respiratory Department, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins; D053449:TNF Receptor-Associated Factor 4 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C513674:Apopt1 protein, mouse; D051017:Apoptosis Regulatory Proteins; C526503:MIRN370 microRNA, human; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D053449:TNF Receptor-Associated Factor 4; C506367:TRAF4 protein, human