title: miR‑338‑3p suppresses tumor growth of ovarian epithelial carcinoma by targeting Runx2.
abstract: miR‑338‑3p, a recently discovered miRNA, has been shown to play important roles in tumorigenesis and metastasis in various cancers. However, the exact roles and mechanisms of miR‑338‑3p remain unknown in human ovarian epithelial carcinoma (EOC). The relationship between miR‑338‑3p expression pattern and clinicopathological features of patients with EOC were determined by real-time quantitative RT-PCR. Furthermore, the role of miR‑338‑3p and possible molecular mechanisms in EOC was investigated by several in vitro approaches and in a nude mouse model. We first showed that the expression of miR‑338‑3p was significantly downregulated in EOC tissues compared to those in adjacent normal tissues, and the value was negatively related to advanced FIGO stage, high histological grading and lymph node metastasis (P<0.01). An in vitro analysis revealed that the overexpression of miR‑338‑3p in EOC cells significantly inhibited cell proliferation, colony formation, migration and invasion, inducing cell apoptosis and enhancing caspase-3, -8, and -9 activities. Bioinformatic analysis and dual luciferase assays identified Runx2 as a direct target of miR‑338‑3p. We also found that enforced expression of miR‑338‑3p markedly inhibited the in vivo tumorigenicity in a nude mouse xenograft model system. Furthermore, overexpression of miR‑338‑3p inhibited phosphorylation of PI3K and AKT, which contributed to suppression of ovarian cancer cell growth. These findings revealed that miR‑338‑3p may act as a tumor suppressor that blocks the growth of human ovarian epithelial carcinoma through PI3K/AKT signaling pathways by targeting Runx2.
authors.affiliation: Department of Pathology, China-Japan Union Hospital of Jilin University, Nanguan District, Changchun 13033, P.R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wen
authors.affiliation: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Nanguan District, Changchun 13033, P.R. China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, The First Hospital of Jilin University, Changchun 130021, P.R. China.
authors.forename: Hongxi
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Pathology, China-Japan Union Hospital of Jilin University, Nanguan District, Changchun 13033, P.R. China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, The First Hospital of Jilin University, Changchun 130021, P.R. China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D002470:Cell Survival / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C532050:MIRN338 microRNA, human; D035683:MicroRNAs; C493709:RUNX2 protein, human