title: MicroRNA-376c suppresses non-small-cell lung cancer cell growth and invasion by targeting LRH-1-mediated Wnt signaling pathway.
abstract: MicroRNAs (miRNAs) that negatively regulate gene expression have emerged as novel therapeutic tools for cancer treatment. In this study, we investigated the potential role of Liver receptor homolog-1 (LRH-1), a novel oncogene, in non-small-cell lung cancer (NSCLC), and examined the regulation of LRH-1 by miRNAs. We found that LRH-1 was highly overexpressed in NSCLC cell lines. Knockdown of LRH-1 by small interfering RNA significantly inhibited NSCLC cell growth and invasion. miR-376c directly targeted the 3'-untranslated region (UTR) of LRH-1 and negatively regulated LRH-1 expression, as detected by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction and Western blot analysis. Further data showed that miR-376c expression was inversely correlated with LRH-1 expression in clinical cancer samples. Overexpression of miR-376c could inhibit NSCLC cell growth and invasion as well as Wnt signaling. In contrast, depletion of miR-376c exhibited the opposite effects. Moreover, these effects of miR-376c overexpression were partially abrogated by overexpression of LRH-1. Taken together, these results indicate that LRH-1 is involved in regulating the growth and invasion of NSCLC cells and that miR-376c inhibits NSCLC cell growth and invasion by targeting LRH-1, providing a novel insight into the potential for development of anti-cancer drugs for NSCLC.
authors.affiliation: Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China. Electronic address: wenjunjiang123@163.com.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Siyang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Xitong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Dali
authors.initials: D
authors.lastname: Tian
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes; D002460:Cell Line; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D009361:Neoplasm Invasiveness; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: C573498:MIRN376C microRNA, human; D035683:MicroRNAs; C082631:NR5A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear
keywords: Liver receptor homolog-1; Non-small-cell lung cancer; Wnt; miR-376c