miR‑653‑5p suppresses the growth and migration of breast cancer cells by targeting MAPK6

Zhang,Mei; Wang,Hongwei; Zhang,Xiaomei; Liu,Fengping

doi:10.3892/mmr.2021.11839

miR‑653‑5p suppresses the growth and migration of breast cancer cells by targeting MAPK6

Authors:
- Mei Zhang
- Hongwei Wang
- Xiaomei Zhang
- Fengping Liu
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Affiliations: Department of Radiotherapy Technology, Linyi Cancer Hospital, Linyi, Shandong 276000, P.R China, Department of Operating Theatre, Linyi Cancer Hospital, Linyi, Shandong 276000, P.R China, Department of Gynaecology, Linyi Cancer Hospital, Linyi, Shandong 276000, P.R China
Published online on: January 12, 2021 https://doi.org/10.3892/mmr.2021.11839
Article Number: 200
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is the worldwide leading cause of cancer‑related deaths among women. Increasing evidence has demonstrated that microRNAs (miRNAs) play critical roles in the carcinogenesis and progression of breast cancer. miR‑653‑5p was previously reported to be involved in cell proliferation and apoptosis. However, the role of miR‑653‑5p in the progression of breast cancer has not been studied. In the present study, it was found that overexpression of miR‑653‑5p significantly inhibited the proliferation, migration and invasion of breast cancer cells in vitro. Moreover, overexpression of miR‑653‑5p promoted cell apoptosis in breast cancer by regulating the Bcl‑2/Bax axis and caspase‑9 activation. Additionally, the epithelial‑mesenchymal transition and activation of the Akt/mammalian target of rapamycin signaling pathway were also inhibited by miR‑653‑5p. Furthermore, the data demonstrated that miR‑653‑5p directly targeted mitogen‑activated protein kinase 6 (MAPK6) and negatively regulated its expression in breast cancer cells. Upregulation of MAPK6 could overcome the inhibitory effects of miR‑653‑5p on cell proliferation and migration in breast cancer. In conclusion, this study suggested that miR‑653‑5p functions as a tumor suppressor by targeting MAPK6 in the progression of breast cancer, and it may be a potential target for breast cancer therapy.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Israel BB, Tilghman SL, Parker-Lemieux K and Payton-Stewart F: Phytochemicals: Current strategies for treating breast cancer. Oncol Lett. 15:7471–7478. 2018.PubMed/NCBI
3	Calaf GM and Roy D: Metastatic genes targeted by an antioxidant in an established radiation- and estrogen-breast cancer model. Int J Oncol. 51:1590–1600. 2017. View Article : Google Scholar : PubMed/NCBI
4	Cristofanilli M and Fortina P: Circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 369:932013. View Article : Google Scholar : PubMed/NCBI
5	Si W, Shen J, Du C, Chen D, Gu X, Li C, Yao M, Pan J, Cheng J, Jiang D, et al: A miR-20a/MAPK1/c-Myc regulatory feedback loop regulates breast carcinogenesis and chemoresistance. Cell Death Differ. 25:406–420. 2018. View Article : Google Scholar : PubMed/NCBI
6	Chen S, Wang Y, Zhang JH, Xia QJ, Sun Q, Li ZK, Zhang JG, Tang MS and Dong MS: Long non-coding RNA PTENP1 inhibits proliferation and migration of breast cancer cells via AKT and MAPK signaling pathways. Oncol Lett. 14:4659–4662. 2017. View Article : Google Scholar : PubMed/NCBI
7	Fabbri M: TLRs as miRNA receptors. Cancer Res. 72:6333–6337. 2012. View Article : Google Scholar : PubMed/NCBI
8	Torres S, García-Palmero I, Bartolomé RA, Fernandez-Aceñero MJ, Molina E, Calviño E, Segura MF and Casal JI: Combined miRNA profiling and proteomics demonstrates that different miRNAs target a common set of proteins to promote colorectal cancer metastasis. J Pathol. 242:39–51. 2017. View Article : Google Scholar : PubMed/NCBI
9	Garzon R, Marcucci G and Croce CM: Targeting microRNAs in cancer: Rationale, strategies and challenges. Nat Rev Drug Discov. 9:775–789. 2010. View Article : Google Scholar : PubMed/NCBI
10	Rupaimoole R and Slack FJ: MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 16:203–221. 2017. View Article : Google Scholar : PubMed/NCBI
11	Liu X, Bi L, Wang Q, Wen M, Li C, Ren Y, Jiao Q, Mao JH, Wang C, Wei G and Wang Y: miR-1204 targets VDR to promotes epithelial-mesenchymal transition and metastasis in breast cancer. Oncogene. 37:3426–3439. 2018. View Article : Google Scholar : PubMed/NCBI
12	El Helou R, Pinna G, Cabaud O, Wicinski J, Bhajun R, Guyon L, Rioualen C, Finetti P, Gros A, Mari B, et al: miR-600 acts as a bimodal switch that regulates breast cancer stem cell fate through WNT signaling. Cell Rep. 18:2256–2268. 2017. View Article : Google Scholar : PubMed/NCBI
13	Liu W, Xu Y, Guan H and Meng H: Clinical potential of miR-940 as a diagnostic and prognostic biomarker in breast cancer patients. Cancer Biomark. 22:487–493. 2018. View Article : Google Scholar : PubMed/NCBI
14	Cao YL, Dong W, Li YZ and Han W: MicroRNA-653 inhibits thymocyte proliferation and induces thymocyte apoptosis in mice with autoimmune myasthenia gravis by downregulating TRIM9. Neuroimmunomodulation. 26:7–18. 2019. View Article : Google Scholar : PubMed/NCBI
15	Yuan L, Feng Y, Li L, et al: Effect of microRNA-653 on biological characteristics of human non-small cell lung cancer cells by targeting OIP5 gene and regulating mTOR signaling pathway. J Mod Oncol. 26:831–837. 2018.
16	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
17	Tokunaga E, Oki E, Egashira A, Sadanaga N, Morita M, Kakeji Y and Maehara Y: Deregulation of the Akt pathway in human cancer. Curr Cancer Drug Targets. 8:27–36. 2008. View Article : Google Scholar : PubMed/NCBI
18	Paladini L, Fabris L, Bottai G, Raschioni C, Calin GA and Santarpia L: Targeting microRNAs as key modulators of tumor immune response. J Exp Clin Cancer Res. 35:1032016. View Article : Google Scholar : PubMed/NCBI
19	Rupaimoole R, Calin GA, Lopez-Berestein G and Sood AK: miRNA deregulation in cancer cells and the tumor microenvironment. Cancer Discov. 6:235–246. 2016. View Article : Google Scholar : PubMed/NCBI
20	Morgensztern D and McLeod HL: PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs. 16:797–803. 2005. View Article : Google Scholar : PubMed/NCBI
21	Mayer IA and Arteaga CL: The PI3K/AKT pathway as a target for cancer treatment. Annu Rev Med. 67:11–28. 2016. View Article : Google Scholar : PubMed/NCBI
22	Brand F, Schumacher S, Kant S, Menon MB, Simon R, Turgeon B, Britsch S, Meloche S, Gaestel M and Kotlyarov A: The extracellular signal-regulated kinase 3 [mitogen-activated protein kinase 6 (MAPK6)]-MAPK-activated protein kinase 5 signaling complex regulates septin function and dendrite morphology. Mol Cell Biol. 32:2467–2478. 2012. View Article : Google Scholar : PubMed/NCBI
23	Al-Mahdi R, Babteen N, Thillai K, Holt M, Johansen B, Wetting HL, Seternes OM and Wells CM: A novel role for atypical MAPK kinase ERK3 in regulating breast cancer cell morphology and migration. Cell Adh Migr. 9:483–494. 2015. View Article : Google Scholar : PubMed/NCBI
24	Evtimova V, Schwirzke M, Tarbé N, Burtscher H, Jarsch M, Kaul S and Weidle UH: Identification of breast cancer metastasis-associated genes by chip technology. Anticancer Res. 21:3799–3806. 2001.PubMed/NCBI
25	Liang B, Wang S, Zhu XG, Yu YX, Cui ZR and Yu YZ: Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer. World J Gastroenterol. 11:623–628. 2005. View Article : Google Scholar : PubMed/NCBI
26	Long W, Foulds CE, Qin J, Liu J, Ding C, Lonard DM, Solis LM, Wistuba II, Qin J, Tsai SY, et al: ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion. J Clin Invest. 122:1869–1880. 2012. View Article : Google Scholar : PubMed/NCBI
27	Zhou YH, Huang YY and Ma M: MicroRNA-138 inhibits proliferation and induces apoptosis of laryngeal carcinoma via targeting MAPK6. Eur Rev Med Pharmacol Sci. 22:5569–5575. 2018.PubMed/NCBI
28	Wu J, Zhao Y, Li F and Qiao B: MiR-144-3p: A novel tumor suppressor targeting MAPK6 in cervical cancer. J Physiol Biochem. 75:143–152. 2019. View Article : Google Scholar : PubMed/NCBI
29	Lv P, Qiu X, Gu Y, Yang X, Xu X and Yang Y: Long non-coding RNA SNHG6 enhances cell proliferation, migration and invasion by regulating miR-26a-5p/MAPK6 in breast cancer. Biomed Pharmacother. 110:294–301. 2019. View Article : Google Scholar : PubMed/NCBI
30	Potapova O, Gorospe M, Dougherty RH, Dean NM, Gaarde WA and Holbrook NJ: Inhibition of c-Jun N-terminal kinase 2 expression suppresses growth and induces apoptosis of human tumor cells in a p53-dependent manner. Mol Cell Biol. 20:1713–1722. 2000. View Article : Google Scholar : PubMed/NCBI
31	Hu C, Huang S, Wu F and Ding H: miR-98 inhibits cell proliferation and induces cell apoptosis by targeting MAPK6 in HUVECs. Exp Ther Med. 15:2755–2760. 2018.PubMed/NCBI
32	Hao W, Zhao ZH, Meng QT, Tie ME, Lei SQ and Xia ZY: Propofol protects against hepatic ischemia/reperfusion injury via miR-133a-5p regulating the expression of MAPK6. Cell Biol Int. 41:495–504. 2017. View Article : Google Scholar : PubMed/NCBI