title: RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells.
abstract: As the most lethal gynecological malignancy, ovarian cancer has attracted much attention over the past few decades; however, the early detection of this malignancy has been largely unsuccessful. The aim of this study was to determine the effects of Ras-association domain family 1, isoform A (RASSF1A) on ovarian cancer and to elucidate the molecular mechanisms responsible for these effects. The expression of RASSF1A in different ovarian cancer cells was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The morphology, structure, apoptosis and proliferation of differently treated SKOV-3 cells were then analyzed using a fluorescence microscope, transmission electron microscope, flow cytometer and by western blot analysis, respectively. Moreover, the GSE14407 affymetrix microarray data were downloaded from the Gene Expression Omnibus database and the expression of RASSF1A was quantified by Spotfire DecisionSite software. A RASSF1A related protein-protein interaction (PPI) network was then constructed using STRING and Cytoscape software. Finally, DAVID was utilized to perform KEGG pathway enrichment analysis of the network. RASSF1A was expressed in the HO8910, HO8910PM cells and the SKOV-3 cells transfected with RASSF1A, whereas it was absent in the other SKOV-3 cells and OVCAR-3 cells. Additionally, compared with the other SKOV-3 cells, the nucleus of SKOV-3 cells transfected with RASSF1A was vacuolated, apoptosis was increased, and the expression of cyclin D1 and survivin was decreased (P<0.05), and that of p27 and caspase-3 was increased (P<0.01). Additionally, 10 genes, including serine/threonine kinase (STK)3, STK4, Harvey rat sarcoma viral oncogene homolog (HRAS) and cell division cycle 20 (CDC20), were found to have close interactions with RASSF1A in the PPI network. Finally, a total of 8 enriched pathways, such as bladder cancer, non-small cell lung cancer and pathways in cancer were identified. To our knowledge, this is the first study to explore the biological functions and the underlying mechanisms of action of RASSF1A in the development of ovarian cancer. Our findings may provide a novel therapeutic target for ovarian cancer.
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Lingjie
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Shulan
authors.initials: S
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins