title: miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma.
abstract: High-grade serous ovarian carcinoma (HGSOC), the most common and aggressive subtype of epithelial ovarian cancer, is characterized by TP53 mutations and genetic instability. Using miRNA profiling analysis, we found that miR-145, a p53 regulated miRNA, was frequently down-regulated in HGSOC. miR-145 down-regulation was further validated in a large cohort of HGSOCs by qPCR. Overexpression of miR-145 in ovarian cancer cells significantly suppressed proliferation, migration and invasion in vitro and inhibited tumor growth and metastasis in vivo. Metadherin (MTDH) was subsequently identified as a direct target of miR-145, and was found to be significantly up-regulated in HGSOC. Furthermore, overexpression of MTDH rescued the inhibitory effects of miR-145 in ovarian cancer cells. Finally, we found that high level of MTDH expression correlated with poor prognosis of HGSOC. Therefore, lack of suppression of MTDH by miR-145 when p53 is dysfunctional leads to increased tumor growth and metastasis of HGSOC. Our study established a new link between p53, miR-145 and MTDH in the regulation of tumor growth and metastasis in HGSOC.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Ruifen
authors.initials: R
authors.lastname: Dong
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yinuo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology, Northwestern University School of Medicine, Chicago, IL, USA.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wei
authors.affiliation: Ministry of Education Key Laboratory of Experimental Teratology and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, China.
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D017931:DNA Primers / Q000737:chemistry; D005185:Fallopian Tube Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D015815:Cell Adhesion Molecules; D017931:DNA Primers; C541010:MIRN145 microRNA, human; C483039:MTDH protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins