Methylation-mediated repression of MiR-424/503 cluster promotes proliferation and migration of ovarian cancer cells through targeting the hub gene KIF23

Tong Li; Yimin Li; Yaqi Gan; Ruotong Tian; Qihan Wu; Guang Shu; Gang Yin

doi:10.1080/15384101.2019.1624112

Methylation-mediated repression of MiR-424/503 cluster promotes proliferation and migration of ovarian cancer cells through targeting the hub gene KIF23

Cell Cycle. 2019 Jul;18(14):1601-1618. doi: 10.1080/15384101.2019.1624112. Epub 2019 Jun 9.

Authors

Tong Li¹, Yimin Li¹, Yaqi Gan¹, Ruotong Tian², Qihan Wu³, Guang Shu², Gang Yin¹

Affiliations

¹ a Department of Pathology , Xiangya Hospital, School of Basic Medical Sciences, Central South University , Changsha , Hunan Province , China.
² b School of Basic Medical Sciences , Central South University , Changsha , Hunan Province , China.
³ c NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Medical School , Fudan University , Shanghai , China.

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

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions
Carcinogenesis / genetics
Carcinoma, Ovarian Epithelial / genetics*
Carcinoma, Ovarian Epithelial / metabolism
Carcinoma, Ovarian Epithelial / pathology
Cell Cycle / genetics
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation / genetics
DNA Methylation
Databases, Nucleic Acid
Female
Gene Expression Regulation, Neoplastic / genetics
Humans
MicroRNAs / chemistry
MicroRNAs / genetics*
MicroRNAs / metabolism
Microtubule-Associated Proteins / genetics*
Microtubule-Associated Proteins / metabolism
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology
Promoter Regions, Genetic
Protein Interaction Maps

Substances

3' Untranslated Regions
KIF23 protein, human
MIRN424 microrna, human
MIRN503 microRNA, human
MicroRNAs
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].