Methylation-mediated Repression of MiR-424/503 Cluster Promotes Proliferation and Migration of Ovarian Cancer Cells Through Targeting the Hub Gene KIF23

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2019 May 29

PMID 31135262

Citations 30

Authors

Tong Li

Yimin Li

Yaqi Gan

Ruotong Tian

Qihan Wu

Guang Shu

Gang Yin

Affiliations

Soon will be listed here.

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.

Citing Articles

Unraveling the extracellular vesicle network: insights into ovarian cancer metastasis and chemoresistance.

Dai W, Zhou J, Chen T Mol Cancer. 2024; 23(1):201.

PMID: 39285475 PMC: 11404010. DOI: 10.1186/s12943-024-02103-x.

Jia W, Li N, Wang J, Gong X, Ouedraogo S, Wang Y EPMA J. 2024; 15(2):375-404.

PMID: 38841623 PMC: 11148001. DOI: 10.1007/s13167-024-00359-3.

Tweety homolog 3 promotes colorectal cancer progression through mutual regulation of histone deacetylase 7.

Lu P, Deng S, Liu J, Xiao Q, Zhou Z, Li S MedComm (2020). 2024; 5(6):e576.

PMID: 38827027 PMC: 11141500. DOI: 10.1002/mco2.576.

SIRT7 promotes the proliferation and migration of anaplastic thyroid cancer cells by regulating the desuccinylation of KIF23.

Wu Y, Chen W, Miao H, Xu T BMC Cancer. 2024; 24(1):210.

PMID: 38360598 PMC: 10870498. DOI: 10.1186/s12885-024-11965-9.

Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors.

Timofeeva A, Fedorov I, Asaturova A, Sannikova M, Tregubova A, Mayboroda O Int J Mol Sci. 2023; 24(15).

PMID: 37569592 PMC: 10419267. DOI: 10.3390/ijms241512214.

References

Sablin E . Kinesins and microtubules: their structures and motor mechanisms. Curr Opin Cell Biol. 2000; 12(1):35-41. DOI: 10.1016/s0955-0674(99)00054-x. View

Kamimoto T, Zama T, Aoki R, Muro Y, Hagiwara M . Identification of a novel kinesin-related protein, KRMP1, as a target for mitotic peptidyl-prolyl isomerase Pin1. J Biol Chem. 2001; 276(40):37520-8. DOI: 10.1074/jbc.M106207200. View

Kline-Smith S, Walczak C . Mitotic spindle assembly and chromosome segregation: refocusing on microtubule dynamics. Mol Cell. 2004; 15(3):317-27. DOI: 10.1016/j.molcel.2004.07.012. View

Glotzer M . The molecular requirements for cytokinesis. Science. 2005; 307(5716):1735-9. DOI: 10.1126/science.1096896. View

Naora H, Montell D . Ovarian cancer metastasis: integrating insights from disparate model organisms. Nat Rev Cancer. 2005; 5(5):355-66. DOI: 10.1038/nrc1611. View

Miki H, Okada Y, Hirokawa N . Analysis of the kinesin superfamily: insights into structure and function. Trends Cell Biol. 2005; 15(9):467-76. DOI: 10.1016/j.tcb.2005.07.006. View

Neef R, Klein U, Kopajtich R, Barr F . Cooperation between mitotic kinesins controls the late stages of cytokinesis. Curr Biol. 2006; 16(3):301-7. DOI: 10.1016/j.cub.2005.12.030. View

Esquela-Kerscher A, Slack F . Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006; 6(4):259-69. DOI: 10.1038/nrc1840. View

Huszar D, Theoclitou M, Skolnik J, Herbst R . Kinesin motor proteins as targets for cancer therapy. Cancer Metastasis Rev. 2009; 28(1-2):197-208. DOI: 10.1007/s10555-009-9185-8. View

10.

Bast Jr R, Hennessy B, Mills G . The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009; 9(6):415-28. PMC: 2814299. DOI: 10.1038/nrc2644. View

11.

Bandres E, Agirre X, Bitarte N, Ramirez N, Zarate R, Roman-Gomez J . Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer. 2009; 125(11):2737-43. DOI: 10.1002/ijc.24638. View

12.

Yang G, Chang B, Yang F, Guo X, Cai K, Xiao X . Aurora kinase A promotes ovarian tumorigenesis through dysregulation of the cell cycle and suppression of BRCA2. Clin Cancer Res. 2010; 16(12):3171-81. PMC: 2930838. DOI: 10.1158/1078-0432.CCR-09-3171. View

13.

de Souza Rocha Simonini P, Breiling A, Gupta N, Malekpour M, Youns M, Omranipour R . Epigenetically deregulated microRNA-375 is involved in a positive feedback loop with estrogen receptor alpha in breast cancer cells. Cancer Res. 2010; 70(22):9175-84. DOI: 10.1158/0008-5472.CAN-10-1318. View

14.

Kunej T, Godnic I, Ferdin J, Horvat S, Dovc P, Calin G . Epigenetic regulation of microRNAs in cancer: an integrated review of literature. Mutat Res. 2011; 717(1-2):77-84. DOI: 10.1016/j.mrfmmm.2011.03.008. View

15.

Takahashi S, Fusaki N, Ohta S, Iwahori Y, Iizuka Y, Inagawa K . Downregulation of KIF23 suppresses glioma proliferation. J Neurooncol. 2011; 106(3):519-29. DOI: 10.1007/s11060-011-0706-2. View

16.

Rissland O, Hong S, Bartel D . MicroRNA destabilization enables dynamic regulation of the miR-16 family in response to cell-cycle changes. Mol Cell. 2011; 43(6):993-1004. PMC: 3202612. DOI: 10.1016/j.molcel.2011.08.021. View

17.

He Y, Cui Y, Wang W, Gu J, Guo S, Ma K . Hypomethylation of the hsa-miR-191 locus causes high expression of hsa-mir-191 and promotes the epithelial-to-mesenchymal transition in hepatocellular carcinoma. Neoplasia. 2011; 13(9):841-53. PMC: 3182276. DOI: 10.1593/neo.11698. View

18.

Nislow C, Sellitto C, Kuriyama R, McIntosh J . A monoclonal antibody to a mitotic microtubule-associated protein blocks mitotic progression. J Cell Biol. 1990; 111(2):511-22. PMC: 2116221. DOI: 10.1083/jcb.111.2.511. View

19.

Minor J, Wang X, Zhang F, Song J, Jimeno A, Wang X . Methylation of microRNA-9 is a specific and sensitive biomarker for oral and oropharyngeal squamous cell carcinomas. Oral Oncol. 2011; 48(1):73-8. PMC: 3291120. DOI: 10.1016/j.oraloncology.2011.11.006. View

20.

Klopp A, Zhang Y, Solley T, Amaya-Manzanares F, Marini F, Andreeff M . Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors. Clin Cancer Res. 2011; 18(3):771-82. PMC: 3481843. DOI: 10.1158/1078-0432.CCR-11-1916. View