title: MicroRNA-361-3p suppresses tumor cell proliferation and metastasis by directly targeting SH2B1 in NSCLC.
abstract: BACKGROUND
  Lung cancer is the most common malignancies worldwide. However, the detailed molecular mechanisms underlying lung cancer progression are still not completely clear. MicroRNAs are small noncoding RNAs which occupy a crucial role of cancer metastasis. Accumulating evidence suggests that miR-361 plays important roles in human carcinogenesis. However, its precise biological role remains largely elusive, especially in lung cancer. This study examined the role of miR-361-3p in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Real-time quantitative PCR (qRT-PCR) was used to analyze the expression of miR-361-3p in NSCLC tissue and in compared adjacent non-cancerous tissues. The effect of miR-361-3p on proliferation was evaluated by CCK8 and colony formation assays. The effect of miR-361-3p on migration and invasion was evaluated by transwell assays. Western blotting and immunohistochemical staining were applied to analyze the expression of target proteins and downstream molecule, and the luciferase reporter assay to assess the target genes of miR-361-3p in non-small cell lung cancer cells.
  
  
  RESULTS
  miR-361-3p was significantly decreased in NSCLC tissue and cell lines, and its expression levels were highly correlated with lymph node metastasis (P < 0.01) and TNM stages (P < 0.05). Down-regulation of miR-361-3p promoted cell growth, proliferation, colony formation, invasion and migration in vitro, and promoted proliferation and metastasis in vivo (P < 0.01); whereas up-regulation of miR-361-3p had the contrary effects. The luciferase reporter assay showed that SH2B1 was a direct target gene of miR-361-3p. Enforced expression of miR-361-3p inhibited the expression of SH2B1 significantly and the restoration of SH2B1 expression reversed the inhibitory effects of miR-361-3p on NSCLC cell proliferation and metastasis.
  
  
  CONCLUSIONS
  miR-361-3p functions as a novel tumor suppressor in NSCLC and the anti-oncogenic activity may involve its inhibition of the target gene SH2B1. These findings suggest the possibility for miR-361-3p as a therapeutic target in NSCLC.
authors.affiliation: Department of Thoracic Surgery, Xiangya Hospital, Central South University, Xiangya Road 87th, Changsha, 410008, Hunan, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Institute of Medical Sciences, Xiangya Hospital, Central South University, Xiangya Road 87th, Changsha, 410008, Hunan, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology Surgery, Xiangya Hospital, Central South University, Xiangya Road 87th, Changsha, 410008, Hunan, PR China.
authors.forename: Sulai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Xiangya Hospital, Central South University, Xiangya Road 87th, Changsha, 410008, Hunan, PR China.
authors.forename: Shaoqiang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Xiangya Hospital, Central South University, Xiangya Road 87th, Changsha, 410008, Hunan, PR China.
authors.forename: Yuanda
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Thoracic Surgery, Xiangya Hospital, Central South University, Xiangya Road 87th, Changsha, 410008, Hunan, PR China.
authors.forename: Wolong
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Institute of Medical Sciences, Xiangya Hospital, Central South University, Xiangya Road 87th, Changsha, 410008, Hunan, PR China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Duan
authors.affiliation: Department of Thoracic Surgery, Xiangya Hospital, Central South University, Xiangya Road 87th, Changsha, 410008, Hunan, PR China. zcf6636169@sina.com.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C575475:MIRN361 microRNA, human; D035683:MicroRNAs; C518910:SH2B1 protein, human
keywords: NSCLC; Progression; SH2B1; miR-361-3p