title: MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway.
abstract: MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3'-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5p overexpression significantly decreased the Wnt/β-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.
authors.affiliation: Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Endoscopic Center, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, P.R. China.
authors.forename: Jingrong
authors.initials: J
authors.lastname: Dong
authors.affiliation: Endoscopic Center, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, P.R. China.
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C578248:MIRN219 microRNA, human; D035683:MicroRNAs; C082631:NR5A2 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D051153:Wnt Proteins; D051176:beta Catenin