title: MicroRNA-383 is a tumor suppressor in human lung cancer by targeting endothelial PAS domain-containing protein 1.
abstract: Lung cancer is the deadliest of all human cancers worldwide. The role of microRNA (miR)-383 has been controversial in the initiation and progression of different cancers. We aimed to investigate the function of miR-383 in human lung cancer both in vitro and in vivo. MicroRNA-383 levels were analyzed in noncancerous versus cancerous human lung tissues and in normal versus lung cancer cell lines. Effect of miR-383 on cell migration and invasion was examined in vitro and on tumor growth by using a xenograft mouse model in vivo. Potential mRNA target of miR-383 was predicted, and underlying mechanism was explored as well. MicroRNA-383 was downregulated in lung cancer tissue and cell lines. Expression of miR-383 inhibited migration and invasion of human lung cancer cell lines in vitro and tumorigenesis of lung cancer xenografts in vivo. MicroRNA-383 directly targeted 3' untranslated region of endothelial PAS domain-containing protein 1 (EPAS1) messenger RNA and inhibited both its mRNA and protein expressions. Reintroduction of EPAS1 could bypass the inhibition by miR-383 on tumorigenesis of human lung cancer cell lines. MicroRNA-383 is a tumor suppressor in human lung cancer by inhibiting EPAS1, both of which could serve as potential therapeutic targets in the treatment of lung cancer.
  
  
  CONCLUSIONS
  MicroRNA-383 is a tumor suppressor in human lung cancer, which functions to inhibit tumorigenesis of lung cancer cells both in vitro and in vivo. This inhibitory effect is mediated by direct targeting of EPAS1 mRNA and subsequent repressing of its expression. Both microRNA-383 and EPAS1 could serve as potential therapeutic targets in the treatment of lung cancer.
authors.affiliation: Department of Respiratory Medicine, The Fifth Central Hospital in Tianjin, Tianjin, China.
authors.forename: Hongjing
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Emergency, The Fifth Central Hospital in Tianjin, Tianjin, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The Fifth Central Hospital in Tianjin, Tianjin, China.
authors.forename: Shuoying
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, The Fifth Central Hospital in Tianjin, Tianjin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D020413:3' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D000099162:Endothelial PAS Domain-Containing Protein 1; C558685:MIRN383 microRNA, human
keywords: endothelial PAS domain-containing protein 1; lung cancer; microRNA-383; mouse xenograft; tumor suppressor