title: MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer.
abstract: Ovarian carcinoma is the most lethal gynaecological malignancy. Better understanding of the molecular pathogenesis of this disease and effective targeted therapies are needed to improve patient outcomes. MicroRNAs play important roles in cancer progression and have the potential for use as either therapeutic agents or targets. Studies in other cancers have suggested that miR-506 has anti-tumour activity, but its function has yet to be elucidated. We found that deregulation of miR-506 in ovarian carcinoma promotes an aggressive phenotype. Ectopic over-expression of miR-506 in ovarian cancer cells was sufficient to inhibit proliferation and to promote senescence. We also demonstrated that CDK4 and CDK6 are direct targets of miR-506, and that miR-506 can inhibit CDK4/6-FOXM1 signalling, which is activated in the majority of serous ovarian carcinomas. This newly recognized miR-506-CDK4/6-FOXM1 axis provides further insight into the pathogenesis of ovarian carcinoma and identifies a potential novel therapeutic agent.
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, People's Republic of China.
authors.forename: Guoyan
authors.initials: G
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Cogdell
authors.forename: Da
authors.initials: D
authors.lastname: Yang
authors.forename: Brittany C
authors.initials: BC
authors.lastname: Parker Kerrigan
authors.forename: Ilya
authors.initials: I
authors.lastname: Shmulevich
authors.forename: Kexin
authors.initials: K
authors.lastname: Chen
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Fengxia
authors.initials: F
authors.lastname: Xue
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D016922:Cellular Senescence; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism*; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C561508:MIRN506 microRNA, human; D035683:MicroRNAs; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6
keywords: FOXM1; miR-506; ovarian carcinoma; proliferation; senescence