Non‑SMC condensin I complex subunit H promotes the malignant progression and cisplatin resistance of breast cancer MCF‑7 cells

Liao,Linhong; Cheng,Hui; Liu,Shusong

doi:10.3892/ol.2022.13438

Non‑SMC condensin I complex subunit H promotes the malignant progression and cisplatin resistance of breast cancer MCF‑7 cells

Authors:
- Linhong Liao
- Hui Cheng
- Shusong Liu
View Affiliations

Affiliations: Department of Pathology, Ganzhou Maternal and Child Health Hospital, Ganzhou, Jiangxi 341000, P.R. China, Department of Emergency, Ganzhou People's Hospital, Ganzhou, Jiangxi 341000, P.R. China, Department of Oncology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 710100, P.R. China
Published online on: July 19, 2022 https://doi.org/10.3892/ol.2022.13438
Article Number: 317
Copyright: © Liao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Abstract. Breast cancer is one of the most frequently diagnosed types of cancer worldwide. The present study aimed to investigate the role and underlying regulatory mechanism of non‑structural maintenance of chromosome condensin I complex subunit H (NCAPH) in the malignant progression and cisplatin (DDP) resistance of breast cancer cells. Therefore, the mRNA and protein expression levels of NCAPH were first determined in breast cancer cells via reverse transcription‑quantitative PCR and western blotting. Furthermore, following transfection of NCAPH interference plasmids, the effect of NCAPH knockdown on cell proliferation, migration, invasion were also assessed using CCK‑8, wound healing and Transwell assays. Apoptosis was evaluated using TUNEL assay, and western blotting was performed in breast cancer cells and DDP‑resistant breast cancer cells. The association between NCAPH and its downstream target, aurora kinase B (AURKB), was verified using bioinformatic analysis and the co‑immunoprecipitation assay. Furthermore, the effect of AURKB overexpression on the aforementioned processes and the Akt/mTOR signaling pathway were also assessed. The results demonstrated that NCAPH mRNA and protein expression levels were significantly upregulated in breast cancer cells, whereas NCAPH knockdown significantly attenuated the proliferation, migration and invasion of breast cancer cells. NCAPH silencing also exacerbated the apoptosis of DDP‑resistant breast cancer cells. AURKB mRNA and protein expression levels were also significantly upregulated in MCF‑7 cells, whereas its overexpression significantly reversed the effects of NCAPH knockdown on breast cancer cells and the Akt/mTOR signaling pathway. Overall, NCAPH knockdown significantly downregulated AURKB mRNA and protein expression levels to block the Akt/mTOR signaling pathway and inhibited breast cancer cell proliferation, migration, invasion, and aggravate DDP‑resistant breast cancer cell apoptosis, indicating that NCAPH may serve as a promising therapeutic target for breast cancer.

View Figures

View References

1	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
2	Pruitt SL, Zhu H, Heitjan DF, Rahimi A, Maddineni B, Tavakkoli A, Halm EA, Gerber DE, Xiong D and Murphy CC: Survival of women diagnosed with breast cancer and who have survived a previous cancer. Breast Cancer Res Treat. 187:853–865. 2021. View Article : Google Scholar : PubMed/NCBI
3	Hendrick RE, Helvie MA and Monticciolo DL: Breast cancer mortality rates have stopped declining in U.S. women younger than 40 years. Radiology. 299:143–149. 2021. View Article : Google Scholar : PubMed/NCBI
4	Tchounwou PB, Dasari S, Noubissi FK, Ray P and Kumar S: Advances in our understanding of the molecular mechanisms of action of cisplatin in cancer therapy. J Exp Pharmacol. 13:303–328. 2021. View Article : Google Scholar : PubMed/NCBI
5	Liu L and Bian K: Advance in studies on molecular mechanisms of cisplatin resistance and intervention with traditional Chinese medicines. Zhongguo Zhong Yao Za Zhi. 39:3216–3220. 2014.(In Chinese). PubMed/NCBI
6	Wang S, Li MY, Liu Y, Vlantis AC, Chan JY, Xue L, Hu BG, Yang S, Chen MX, Zhou S, et al: The role of microRNA in cisplatin resistance or sensitivity. Expert Opin Ther Targets. 24:885–897. 2020. View Article : Google Scholar : PubMed/NCBI
7	Safi A, Bastami M, Delghir S, Ilkhani K, Seif F and Alivand MR: miRNAs modulate the dichotomy of cisplatin resistance or sensitivity in breast cancer: An update of therapeutic implications. Anticancer Agents Med Chem. 21:1069–1081. 2021. View Article : Google Scholar : PubMed/NCBI
8	Hatzidaki E, Daikopoulou V, Apostolou P, Ntanovasilis DA and Papasotiriou I: Increased breast cancer cell sensitivity to cisplatin using a novel small molecule inhibitor. J Cancer Res Ther. 16:1393–1401. 2020.PubMed/NCBI
9	Sun Y, Wang X, Wen H, Zhu B and Yu L: Expression and clinical significance of the NCAPH, AGGF1, and FOXC2 proteins in serous ovarian cancer. Cancer Manag Res. 13:7253–7262. 2021. View Article : Google Scholar : PubMed/NCBI
10	Kim JH, Youn Y, Kim KT, Jang G and Hwang JH: Non-SMC condensin I complex subunit H mediates mature chromosome condensation and DNA damage in pancreatic cancer cells. Sci Rep. 9:178892019. View Article : Google Scholar : PubMed/NCBI
11	Qiu X, Gao Z, Shao J and Li H: NCAPH is upregulated in endometrial cancer and associated with poor clinicopathologic characteristics. Ann Hum Genet. 84:437–446. 2020. View Article : Google Scholar : PubMed/NCBI
12	Kim B, Kim SW, Lim JY and Park SJ: NCAPH is required for proliferation, migration and invasion of non-small-cell lung cancer cells. Anticancer Res. 40:3239–3246. 2020. View Article : Google Scholar : PubMed/NCBI
13	Lu H, Shi C, Wang S, Wan X, Luo Y, Tian L and Li L: Identification of NCAPH as a biomarker for prognosis of breast cancer. Mol Biol Rep. 47:7831–7842. 2020. View Article : Google Scholar : PubMed/NCBI
14	Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, Doncheva NT, Legeay M, Fang T, Bork P, et al: The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 49((D1)): D605–D612. 2021. View Article : Google Scholar : PubMed/NCBI
15	Greene CS, Krishnan A, Wong AK, Ricciotti E, Zelaya RA, Himmelstein DS, Zhang R, Hartmann BM, Zaslavsky E, Sealfon SC, et al: Understanding multicellular function and disease with human tissue-specific networks. Nat Genet. 47:569–576. 2015. View Article : Google Scholar : PubMed/NCBI
16	Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, et al: The GeneMANIA prediction server: Biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 38(Web Server Issue). W214–W220. 2010. View Article : Google Scholar : PubMed/NCBI
17	Tang Z, Li C, Kang B, Gao G, Li C and Zhang Z: GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45((W1)): W98–W102. 2017. View Article : Google Scholar : PubMed/NCBI
18	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
19	Loibl S, Poortmans P, Morrow M, Denkert C and Curigliano G: Breast cancer. Lancet. 397:1750–1769. 2021. View Article : Google Scholar : PubMed/NCBI
20	Raigon-Ponferrada A, Recio MED, Guerrero-Orriach JL, Malo-Manso A, Escalona-Belmonte JJ, Aliaga MR, Fernández AR, García FJF, Conejo EA and Cruz-Mañas J: Breast cancer and anesthesia. Curr Pharm Des. 25:2998–3004. 2019. View Article : Google Scholar : PubMed/NCBI
21	Waks AG and Winer EP: Breast cancer treatment: A review. JAMA. 321:288–300. 2019. View Article : Google Scholar : PubMed/NCBI
22	Wöckel A, Albert US, Janni W, Scharl A, Kreienberg R and Stüber T: The screening, diagnosis, treatment, and follow-up of breast cancer. Dtsch Arztebl Int. 115:316–323. 2018.PubMed/NCBI
23	Harbeck N and Gnant M: Breast cancer. Lancet. 389:1134–1150. 2017. View Article : Google Scholar : PubMed/NCBI
24	Abdel-Hafiz HA: Epigenetic mechanisms of tamoxifen resistance in luminal breast cancer. Diseases. 5:162017. View Article : Google Scholar : PubMed/NCBI
25	Yu S, Kim T, Yoo KH and Kang K: The T47D cell line is an ideal experimental model to elucidate the progesterone-specific effects of a luminal A subtype of breast cancer. Biochem Biophys Res Commun. 486:752–758. 2017. View Article : Google Scholar : PubMed/NCBI
26	Marima R, Hull R, Penny C and Dlamini Z: Mitotic syndicates Aurora Kinase B (AURKB) and mitotic arrest deficient 2 like 2 (MAD2L2) in cohorts of DNA damage response (DDR) and tumorigenesis. Mutat Res Rev Mutat Res. 787:1083762021. View Article : Google Scholar : PubMed/NCBI
27	Xiao J and Zhang Y: AURKB as a promising prognostic biomarker in hepatocellular carcinoma. Evol Bioinform Online. 17:117693432110575892021. View Article : Google Scholar : PubMed/NCBI
28	Nie M, Wang Y, Yu Z, Li X, Deng Y, Wang Y, Yang D, Li Q, Zeng X, Ju J, et al: AURKB promotes gastric cancer progression via activation of CCND1 expression. Aging (Albany NY). 12:1304–1321. 2020. View Article : Google Scholar : PubMed/NCBI
29	Tada K, Susumu H, Sakuno T and Watanabe Y: Condensin association with histone H2A shapes mitotic chromosomes. Nature. 474:477–483. 2011. View Article : Google Scholar : PubMed/NCBI
30	Wang Z, Yu Z, Wang GH, Zhou YM, Deng JP, Feng Y, Chen JQ and Tian L: AURKB promotes the metastasis of gastric cancer, possibly by inducing EMT. Cancer Manag Res. 12:6947–6958. 2020. View Article : Google Scholar : PubMed/NCBI
31	Yu J, Zhou J, Xu F, Bai W and Zhang W: High expression of Aurora-B is correlated with poor prognosis and drug resistance in non-small cell lung cancer. Int J Biol Markers. 33:215–221. 2018. View Article : Google Scholar : PubMed/NCBI
32	Mossmann D, Park S and Hall MN: mTOR signalling and cellular metabolism are mutual determinants in cancer. Nat Rev Cancer. 18:744–757. 2018. View Article : Google Scholar : PubMed/NCBI
33	Alzahrani AS: PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside. Semin Cancer Biol. 59:125–132. 2019. View Article : Google Scholar : PubMed/NCBI
34	Wang C, Chen J, Cao W, Sun L, Sun H and Liu Y: Aurora-B and HDAC synergistically regulate survival and proliferation of lymphoma cell via AKT, mTOR and Notch pathways. Eur J Pharmacol. 779:1–7. 2016. View Article : Google Scholar : PubMed/NCBI