KIF4A knockdown suppresses ovarian cancer cell proliferation and induces apoptosis by downregulating BUB1 expression

Jin,Wumin; Ye,Lianmin

doi:10.3892/mmr.2021.12155

KIF4A knockdown suppresses ovarian cancer cell proliferation and induces apoptosis by downregulating BUB1 expression

Authors:
- Wumin Jin
- Lianmin Ye
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Affiliations: Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: May 17, 2021 https://doi.org/10.3892/mmr.2021.12155
Article Number: 516
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer is one of the most common lethal gynecological malignancies worldwide. Abnormal kinesin family member 4A (KIF4A) expression has been implicated in ovarian cancer progression; however, the potential mechanism underlying KIF4A in ovarian cancer is not completely understood. The present study aimed to clarify the molecular basis of KIF4A in ovarian cancer. KIF4A and budding uninhibited by benzimidazoles 1 (BUB1) expression levels were detected via reverse transcription-quantitative PCR and western blotting. Cell Counting Kit-8, colony formation, wound healing, TUNEL and flow cytometry assays were performed to assess cell proliferation, migration, apoptosis and cell cycle distribution, respectively. Ki67 expression levels were detected by conducting immunofluorescence assays. The expression levels of migration- and apoptosis-related proteins were measured via western blotting. A co-immunoprecipitation assay was conducted to determine the association between KIF4A and BUB1. The results demonstrated that KIF4A was expressed at significantly higher levels in ovarian cancer cell lines compared with IOSE-80 cells. Compared with the short hairpin RNA-negative control group, KIF4A knockdown significantly inhibited cell viability, colony formation and migration, and markedly induced cell apoptosis. The results indicated that KIF4A could bind to BUB1 and regulate BUB1 expression. BUB1 overexpression weakened KIF4A knockdown-mediated effects on cell viability, colony formation, migration and apoptosis. Overall, the present study demonstrated that KIF4A knockdown suppressed ovarian cancer progression by regulating BUB1, and suggested the potential value of KIF4A and BUB1 as therapeutic targets for ovarian cancer.

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1	Webb PM and Jordan SJ: Epidemiology of epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 41:3–14. 2017. View Article : Google Scholar : PubMed/NCBI
2	Stewart C, Ralyea C and Lockwood S: Ovarian Cancer: An Integrated Review. Semin Oncol Nurs. 35:151–156. 2019. View Article : Google Scholar : PubMed/NCBI
3	Vargas AN: Natural history of ovarian cancer. Ecancermedicalscience. 8:4652014.PubMed/NCBI
4	Wang L, Yan W, Li X, Liu Z, Tian T, Chen T, Zou L and Cui Z: S100A10 silencing suppresses proliferation, migration and invasion of ovarian cancer cells and enhances sensitivity to carboplatin. J Ovarian Res. 12:1132019. View Article : Google Scholar : PubMed/NCBI
5	Rath O and Kozielski F: Kinesins and cancer. Nat Rev Cancer. 12:527–539. 2012. View Article : Google Scholar : PubMed/NCBI
6	Ha MJ, Yoon J, Moon E, Lee YM, Kim HJ and Kim W: Assignment of the kinesin family member 4 genes (KIF4A and KIF4B) to human chromosome bands Xq13.1 and 5q33.1 by in situ hybridization. Cytogenet Cell Genet. 88:41–42. 2000. View Article : Google Scholar : PubMed/NCBI
7	Mazumdar M, Sundareshan S and Misteli T: Human chromokinesin KIF4A functions in chromosome condensation and segregation. J Cell Biol. 166:613–620. 2004. View Article : Google Scholar : PubMed/NCBI
8	Hu CK, Coughlin M, Field CM and Mitchison TJ: KIF4 regulates midzone length during cytokinesis. Curr Biol. 21:815–824. 2011. View Article : Google Scholar : PubMed/NCBI
9	Kurasawa Y, Earnshaw WC, Mochizuki Y, Dohmae N and Todokoro K: Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation. EMBO J. 23:3237–3248. 2004. View Article : Google Scholar : PubMed/NCBI
10	Hou PF, Jiang T, Chen F, Shi PC, Li HQ, Bai J and Song J: KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer. Cell Death Dis. 9:4772018. View Article : Google Scholar : PubMed/NCBI
11	Xue D, Cheng P, Han M, Liu X, Xue L, Ye C, Wang K and Huang J: An integrated bioinformatical analysis to evaluate the role of KIF4A as a prognostic biomarker for breast cancer. OncoTargets Ther. 11:4755–4768. 2018. View Article : Google Scholar : PubMed/NCBI
12	Gao H, Chen X, Cai Q, Shang Z and Niu Y: Increased KIF4A expression is a potential prognostic factor in prostate cancer. Oncol Lett. 15:7941–7947. 2018.PubMed/NCBI
13	Hou G, Dong C, Dong Z, Liu G, Xu H, Chen L, Liu L, Wang H and Zhou W: Upregulate KIF4A Enhances Proliferation, Invasion of Hepatocellular Carcinoma and Indicates poor prognosis Across Human Cancer Types. Sci Rep. 7:41482017. View Article : Google Scholar : PubMed/NCBI
14	Yang D, He Y, Wu B, Deng Y, Wang N, Li M and Liu Y: Integrated bioinformatics analysis for the screening of hub genes and therapeutic drugs in ovarian cancer. J Ovarian Res. 13:102020. View Article : Google Scholar : PubMed/NCBI
15	Bolanos-Garcia VM and Blundell TL: BUB1 and BUBR1: Multifaceted kinases of the cell cycle. Trends Biochem Sci. 36:141–150. 2011. View Article : Google Scholar : PubMed/NCBI
16	Fu X, Chen G, Cai ZD, Wang C, Liu ZZ, Lin ZY, Wu YD, Liang YX, Han ZD, Liu JC, et al: Overexpression of BUB1B contributes to progression of prostate cancer and predicts poor outcome in patients with prostate cancer. OncoTargets Ther. 9:2211–2220. 2016.PubMed/NCBI
17	Stahl D, Braun M, Gentles AJ, Lingohr P, Walter A, Kristiansen G and Gütgemann I: Low BUB1 expression is an adverse prognostic marker in gastric adenocarcinoma. Oncotarget. 8:76329–76339. 2017. View Article : Google Scholar : PubMed/NCBI
18	von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P and Snel B: STRING: A database of predicted functional associations between proteins. Nucleic Acids Res. 31:258–261. 2003. View Article : Google Scholar : PubMed/NCBI
19	Feng H, Gu ZY, Li Q, Liu QH, Yang XY and Zhang JJ: Identification of significant genes with poor prognosis in ovarian cancer via bioinformatical analysis. J Ovarian Res. 12:352019. View Article : Google Scholar : PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Wang X and Chen T: CUL4A regulates endometrial cancer cell proliferation, invasion and migration by interacting with CSN6. Mol Med Rep. 23:232021. View Article : Google Scholar : PubMed/NCBI
22	Zhang Y, Yang X, Ge X and Zhang F: Puerarin attenuates neurological deficits via Bcl-2/Bax/cleaved caspase-3 and Sirt3/SOD2 apoptotic pathways in subarachnoid hemorrhage mice. Biomed Pharmacother. 109:726–733. 2019. View Article : Google Scholar : PubMed/NCBI
23	Holschneider CH and Berek JS: Ovarian cancer: Epidemiology, biology, and prognostic factors. Semin Surg Oncol. 19:3–10. 2000. View Article : Google Scholar : PubMed/NCBI
24	Maringe C, Walters S, Butler J, Coleman MP, Hacker N, Hanna L, Mosgaard BJ, Nordin A, Rosen B, Engholm G, et al ICBP Module 1 Working Group, : Stage at diagnosis and ovarian cancer survival: Evidence from the International Cancer Benchmarking Partnership. Gynecol Oncol. 127:75–82. 2012. View Article : Google Scholar : PubMed/NCBI
25	Xu B, Xu T, Liu H, Min Q, Wang S and Song Q: MiR-490-5p suppresses cell proliferation and invasion by targeting BUB1 in hepatocellular carcinoma cells. Pharmacology. 100:269–282. 2017. View Article : Google Scholar : PubMed/NCBI
26	Tang D, Zhao X, Zhang L, Wang Z and Wang C: Identification of hub genes to regulate breast cancer metastasis to brain by bioinformatics analyses. J Cell Biochem. 120:9522–9531. 2019. View Article : Google Scholar : PubMed/NCBI
27	Pabla S, Conroy JM, Nesline MK, Glenn ST, Papanicolau-Sengos A, Burgher B, Hagen J, Giamo V, Andreas J, Lenzo FL, et al: Proliferative potential and resistance to immune checkpoint blockade in lung cancer patients. J Immunother Cancer. 7:272019. View Article : Google Scholar : PubMed/NCBI