Abstract
Ovarian cancer is one type of gynecological malignancies with extremely high lethal rate. Abnormal proliferation and metastasis are regarded to play important roles in patients' death, whereas we know little about the underlying molecular mechanisms. Under this circumstance, our current study aims to investigate the role of hub genes in ovarian cancer. Bioinformatics analysis of the data from GEO and analyses of ovarian cancer samples were performed. Then, the results showed that KIF23, a hub gene, was mainly related to cell cycle and positively associated with poor prognosis. Meanwhile, both miR-424-5p and miR-503-5p directly targeted to 3'UTR of KIF23 to suppress the expression of KIF23 and inhibit ovarian cancer cell proliferation and migration. Furthermore, we discovered that miR-424/503 was epigenetically repressed by hypermethylation in the promoter regions, which directly modulated the expression of KIF23 to improve the oncogenic performance of cancer cells in vitro. Together, our research certifies that miR-424/503 cluster is silenced by DNA hypermethylation, which promotes the expression of KIF23, thereby regulating the proliferation and migration of ovarian cancer cells. Interposing this process might be a novel approach in cancer therapy.
Keywords:
KIF23; Methylation; MiR-424/503 cluster; ovarian cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions
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Carcinogenesis / genetics
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Carcinoma, Ovarian Epithelial / genetics*
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Carcinoma, Ovarian Epithelial / metabolism
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Carcinoma, Ovarian Epithelial / pathology
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Cell Cycle / genetics
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Cell Line, Tumor
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Cell Movement / genetics
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Cell Proliferation / genetics
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DNA Methylation
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Databases, Nucleic Acid
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Female
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Gene Expression Regulation, Neoplastic / genetics
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Humans
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MicroRNAs / chemistry
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Microtubule-Associated Proteins / genetics*
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Microtubule-Associated Proteins / metabolism
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Oligonucleotide Array Sequence Analysis
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Ovarian Neoplasms / genetics*
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / pathology
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Promoter Regions, Genetic
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Protein Interaction Maps
Substances
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3' Untranslated Regions
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KIF23 protein, human
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MIRN424 microrna, human
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MIRN503 microRNA, human
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MicroRNAs
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Microtubule-Associated Proteins
Grants and funding
This work was supported by the National Natural Science Foundation of China [No. 81572900]; The Fundamental Research Funds for the Central Universities of Central South University [No. 1053320171187]; The Fundamental Research Funds for the Central Universities of Central South University [No. 2018zzts232]; National Key R&D Program of China, Stem Cell and Translation Research [No. 2016YFA0102000].