miR‑497 inhibits proliferation and invasion in triple‑negative breast cancer cells via YAP1

Li,Yuan; Hua,Kaiyao; Jin,Jiali; Fang,Lin

doi:10.3892/ol.2021.12841

miR‑497 inhibits proliferation and invasion in triple‑negative breast cancer cells via YAP1

Authors:
- Yuan Li
- Kaiyao Hua
- Jiali Jin
- Lin Fang
View Affiliations

Affiliations: Department of Breast and Thyroid Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213164, P.R. China, School of Medicine, Tongji University, Shanghai 200092, P.R. China, Department of Neurology, Kongjiang Hospital of Yangpu District, Shanghai 200093, P.R. China, Department of Breast and Thyroid Surgery, Shanghai No. 10 People's Hospital, Clinical College of Nanjing Medical University, Shanghai 200072, P.R. China
Published online on: June 2, 2021 https://doi.org/10.3892/ol.2021.12841
Article Number: 580
Copyright: © Li 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

MicroRNA (miR)‑497 has been reported as a tumor suppressor in various cancer types. Nonetheless, the regulation of triple‑negative breast cancer (TNBC) by miR‑497 remains poorly understood. The present study aimed to investigate the potential function and mechanism of miR‑497 in TNBC. A total of 36 TNBC and matched non‑cancerous tissue samples were collected for analysis. Reverse transcription‑quantitative PCR was performed to detect the miR‑497 levels in TNBC tissue. The association between miR‑497 expression, clinical characteristics and survival was then analyzed. To investigate the role of miR‑497 in TNBC, MTT, colony formation, Transwell invasion, cell cycle and cell apoptosis assays were conducted following transfection of miR‑497 mimics into the MDA‑MB‑231 and MDA‑MB‑468 cell lines. Luciferase reporter assays and western blot analysis were used to confirm the regulation of a putative target of miR‑497. The results indicated that the expression of miR‑497 was downregulated in the TNBC specimens. Further analysis demonstrated that the expression of miR‑497 was downregulated in patients with advanced TNBC stages and that low miR‑497 was associated with poor prognosis in patients with TNBC. Transfection of miR‑497 mimics inhibited TNBC cell proliferation and increased cell apoptosis in MDA‑MB‑231 and MDA‑MB‑468 cells. Moreover, cell migration was inhibited following overexpression of miR‑497, which also led to the arrest of the breast cancer cells in the G₀/G₁ phase of the cell cycle. Yes‑associated protein 1 (YAP1), a critical molecule in the Hippo pathway, was identified as a target of miR‑497. Notably, the protein and mRNA expression levels of YAP1 in MDA‑MB‑231 and MDA‑MB‑468 cells were downregulated following overexpression of miR‑497. Overall, the findings of the present study indicated that miR‑497 inhibited TNBC cell proliferation and migration and induced cell apoptosis by negatively regulating YAP1 expression. Thus, targeting miR‑497 may represent a potential strategy for the treatment of TNBC.

View Figures

View References

1	Cardoso F, Harbeck N, Barrios CH, Bergh J, Cortés J, El Saghir N, Francis PA, Hudis CA, Ohno S, Partridge AH, et al: Research needs in breast cancer. Ann Oncol. 28:208–217. 2017. View Article : Google Scholar : PubMed/NCBI
2	Zhai Q, Li H, Sun L, Yuan Y and Wang X: Identification of differentially expressed genes between triple and non-triple-negative breast cancer using bioinformatics analysis. Breast Cancer. 26:784–791. 2019. View Article : Google Scholar : PubMed/NCBI
3	Mouh FZ, Mzibri ME, Slaoui M and Amrani M: Recent progress in triple negative breast cancer research. Asian Pac J Cancer Prev. 17:1595–1608. 2016. View Article : Google Scholar : PubMed/NCBI
4	Yuan Q, Zheng L, Liao Y and Wu G: Overexpression of CCNE1 confers a poorer prognosis in triple-negative breast cancer identified by bioinformatic analysis. World J Surg Oncol. 19:862021. View Article : Google Scholar : PubMed/NCBI
5	Pratama MY, Pascut D, Massi MN and Tiribelli C: The role of microRNA in the resistance to treatment of hepatocellular carcinoma. Ann Transl Med. 7:5772019. View Article : Google Scholar : PubMed/NCBI
6	Ding L, Gu H, Xiong X, Ao H, Cao J, Lin W, Yu M, Lin J and Cui Q: MicroRNAs involved in carcinogenesis, prognosis, therapeutic resistance and applications in human triple-negative breast cancer. Cells. 8:14922019. View Article : Google Scholar : PubMed/NCBI
7	Cheng H, Dong H, Feng J, Tian H, Zhang H and Xu L: miR-497 inhibited proliferation, migration and invasion of thyroid papillary carcinoma cells by negatively regulating YAP1 expression. Onco Targets Ther. 11:4711–4721. 2018. View Article : Google Scholar : PubMed/NCBI
8	Huang Q, Li H, Dai X, Zhao D, Guan B and Xia W: miR-497 inhibits the proliferation and migration of A549 non-small-cell lung cancer cells by targeting FGFR1. Mol Med Rep. 20:3959–3967. 2019.PubMed/NCBI
9	Xu GS, Li ZW, Huang ZP, Brunicardi FC, Jia F, Song C, Zou HJ and Sun RF: MiR-497-5p inhibits cell proliferation and metastasis in hepatocellular carcinoma by targeting insulin-like growth factor 1. Mol Genet Genomic Med. 7:e008602019. View Article : Google Scholar : PubMed/NCBI
10	Wei C, Luo Q, Sun X, Li D, Song H, Li X, Song J, Hua K and Fang L: MicroRNA-497 induces cell apoptosis by negatively regulating Bcl-2 protein expression at the posttranscriptional level in human breast cancer. Int J Clin Exp Pathol. 8:7729–7739. 2015.PubMed/NCBI
11	Li G, Wang K, Wang J, Qin S, Sun X and Ren H: miR-497-5p inhibits tumor cell growth and invasion by targeting SOX5 in non-small-cell lung cancer. J Cell Biochem. 120:10587–10595. 2019. View Article : Google Scholar : PubMed/NCBI
12	Wang L, Li K, Lin X, Yao Z, Wang S, Xiong X, Ning Z, Wang J, Xu X, Jiang Y, et al: Metformin induces human esophageal carcinoma cell pyroptosis by targeting the miR-497/PELP1 axis. Cancer Lett. 450:22–31. 2019. View Article : Google Scholar : PubMed/NCBI
13	Ma W, Feng W, Tan J, Xu A, Hu Y, Ning L, Kang Y, Wang L and Zhao Z: miR-497 may enhance the sensitivity of non-small cell lung cancer cells to gefitinib through targeting the insulin-like growth factor-1 receptor. J Thorac Dis. 10:5889–5897. 2018. View Article : Google Scholar : PubMed/NCBI
14	Overholtzer M, Zhang J, Smolen GA, Muir B, Li W, Sgroi DC, Deng CX, Brugge JS and Haber DA: Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci U S A. 103:12405–12410. 2006. View Article : Google Scholar : PubMed/NCBI
15	Pan D: The hippo signaling pathway in development and cancer. Dev Cell. 19:491–505. 2010. View Article : Google Scholar : PubMed/NCBI
16	Johnson R and Halder G: The two faces of hippo: Targeting the hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov. 13:63–79. 2014. View Article : Google Scholar : PubMed/NCBI
17	Zheng Y and Pan D: The hippo signaling pathway in development and disease. Dev Cell. 50:264–282. 2019. View Article : Google Scholar : PubMed/NCBI
18	Deng X and Fang L: VGLL4 is a transcriptional cofactor acting as a novel tumor suppressor via interacting with TEADs. Am J Cancer Res. 8:932–943. 2018.PubMed/NCBI
19	Hua K, Yang W, Song H, Song J, Wei C, Li D and Fang L: Up-regulation of miR-506 inhibits cell growth and disrupt the cell cycle by targeting YAP in breast cancer cells. Int J Clin Exp Med. 8:12018–12027. 2015.PubMed/NCBI
20	Cao L, Sun PL, Yao M, Jia M and Gao H: Expression of YES-associated protein (YAP) and its clinical significance in breast cancer tissues. Hum Pathol. 68:166–174. 2017. View Article : Google Scholar : PubMed/NCBI
21	Zhu C, Li L, Zhang Z, Bi M, Wang H, Su W, Hernandez K, Liu P, Chen J, Chen M, et al: A non-canonical Role of YAP/TEAD is required for activation of estrogen-regulated enhancers in breast cancer. Mol Cell. 75:791–806.e8. 2019. View Article : Google Scholar : PubMed/NCBI
22	Liu X, Zhou Y, Ning YE, Gu H, Tong Y and Wang N: MiR-195-5p inhibits malignant progression of cervical cancer by targeting YAP1. Onco Targets Ther. 13:931–944. 2020. View Article : Google Scholar : PubMed/NCBI
23	Wang Q, Ding J, Nan G, Lyu Y and Ni G: LncRNA NOC2L-4.1 functions as a tumor oncogene in cervical cancer progression by regulating the miR-630/YAP1 pathway. J Cell Biochem. 120:16913–16920. 2019. View Article : Google Scholar : PubMed/NCBI
24	Hu XH, Dai J, Shang HL, Zhao ZX and Hao YD: miR-1285-3p is a potential prognostic marker in human osteosarcoma and functions as a tumor suppressor by targeting YAP1. Cancer Biomark. 25:1–10. 2019. View Article : Google Scholar : PubMed/NCBI
25	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
26	Thakur V and Kutty RV: Recent advances in nanotheranostics for triple negative breast cancer treatment. J Exp Clin Cancer Res. 38:4302019. View Article : Google Scholar : PubMed/NCBI
27	Piasecka D, Braun M, Kordek R, Sadej R and Romanska H: MicroRNAs in regulation of triple-negative breast cancer progression. J Cancer Res Clin Oncol. 144:1401–1411. 2018. View Article : Google Scholar : PubMed/NCBI
28	Sánchez-González I, Bobien A, Molnar C, Schmid S, Strotbek M, Boerries M, Busch H and Olayioye MA: miR-149 suppresses breast cancer metastasis by blocking paracrine interactions with macrophages. Cancer Res. 80:1330–1341. 2020. View Article : Google Scholar
29	Lee SJ, Jeong JH, Kang SH, Kang J, Kim EA, Lee J, Jung JH, Park HY and Chae YS: MicroRNA-137 inhibits cancer progression by targeting Del-1 in triple-negative breast cancer cells. Int J Mol Sci. 20:61622019. View Article : Google Scholar : PubMed/NCBI
30	Shen L, Li J, Xu L, Ma J, Li H, Xiao X, Zhao J and Fang L: miR-497 induces apoptosis of breast cancer cells by targeting Bcl-w. Exp Ther Med. 3:475–480. 2012. View Article : Google Scholar : PubMed/NCBI
31	Luo QF, Li XY, Gao Y, Long Y, Chen L, Huang YX and Fang L: MiRNA-497 regulates cell growth and invasion by targeting cyclin E1 in breast cancer. Cancer Cell Int. 13:952013. View Article : Google Scholar : PubMed/NCBI
32	Tu Y, Liu L, Zhao D, Liu Y, Ma X, Fan Y, Wan L, Huang T, Cheng Z and Shen B: Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2. Sci Rep. 5:138272015. View Article : Google Scholar : PubMed/NCBI
33	Guo ST, Jiang CC, Wang GP, Li YP, Wang CY, Guo XY, Yang RH, Feng Y, Wang FH, Tseng HY, et al: MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer. Oncogene. 32:1910–1920. 2013. View Article : Google Scholar : PubMed/NCBI
34	Li C, Wang S and Yang C: Long non-coding RNA DLX6-AS1 regulates neuroblastoma progression by targeting YAP1 via miR-497-5p. Life Sci. 11:1176572020. View Article : Google Scholar
35	Duan Y, Zhao M, Jiang M, Li Z and Ni C: LINC02476 promotes the malignant phenotype of hepatocellular carcinoma by sponging miR-497 and increasing HMGA2 expression. Onco Targets Ther. 13:2701–2710. 2020. View Article : Google Scholar : PubMed/NCBI
36	Andrade D, Mehta M, Griffith J, Panneerselvam J, Srivastava A, Kim TD, Janknecht R, Herman T, Ramesh R and Munshi A: YAP1 inhibition radiosensitizes triple negative breast cancer cells by targeting the DNA damage response and cell survival pathways. Oncotarget. 8:98495–98508. 2017. View Article : Google Scholar : PubMed/NCBI
37	Cheng H, Zhang Z, Rodriguez-Barrueco R, Borczuk A, Liu H, Yu J, Silva JM, Cheng SK, Perez-Soler R and Halmos B: Functional genomics screen identifies YAP1 as a key determinant to enhance treatment sensitivity in lung cancer cells. Oncotarget. 7:28976–28988. 2016. View Article : Google Scholar : PubMed/NCBI
38	Guo L, Chen Y, Luo J, Zheng J and Shao G: YAP1 overexpression is associated with poor prognosis of breast cancer patients and induces breast cancer cell growth by inhibiting PTEN. FEBS Open Bio. 9:437–445. 2019. View Article : Google Scholar : PubMed/NCBI
39	Lee JY, Chang JK, Dominguez AA, Lee HP, Nam S, Chang J, Varma S, Qi LS, West RB and Chaudhuri O: YAP-independent mechanotransduction drives breast cancer progression. Nat Commun. 10:18482019. View Article : Google Scholar : PubMed/NCBI
40	Li Z, Ge X, Lu J, Bian M, Li N, Wu X, Li Y, Yan M and Yu J: MiR-141-3p regulates proliferation and senescence of stem cells from apical papilla by targeting YAP. Exp Cell Res. 383:1115622019. View Article : Google Scholar : PubMed/NCBI
41	Chen M, Wu L, Tu J, Zhao Z, Fan X, Mao J, Weng Q, Wu X, Huang L, Xu M and Ji J: miR-590-5p suppresses hepatocellular carcinoma chemoresistance by targeting YAP1 expression. EBioMedicine. 35:142–154. 2018. View Article : Google Scholar : PubMed/NCBI