miR‑148a Suppresses estrogen‑induced viability and migration of breast cancer cells via inhibition of estrogen receptor α expression

Ma,Fang; Feng,Yeqian; Li,Weihui; Li,Zexuan; Liu,Tiebang; Li,Lingjiang

doi:10.3892/etm.2017.4255

miR‑148a Suppresses estrogen‑induced viability and migration of breast cancer cells via inhibition of estrogen receptor α expression

Authors:
- Fang Ma
- Yeqian Feng
- Weihui Li
- Zexuan Li
- Tiebang Liu
- Lingjiang Li
View Affiliations

Affiliations: Mental Health Institute, The Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan, Central South University, Changsha, Hunan 410011, P.R. China, Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, Guangdong 518020, P.R. China
Published online on: March 22, 2017 https://doi.org/10.3892/etm.2017.4255
Pages: 2515-2522

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

MicroRNAs (miRs) play critical roles in the development and malignant progression of human cancers. miR-148a has previously been found to inhibit the migration and invasion of breast cancer cells. However, the underlying mechanism of miR‑148a in regulating the viability and migration of estrogen receptor (ER) α‑positive breast cancer cells is still unknown. In this study, ERα‑positive breast cancer MCF7 cells were treated with estradiol (E2). Data from MTT and wound healing assays showed that E2 treatment promoted the viability and migration of MCF7 cells. A bioinformatics analysis and luciferase reporter assay identified ERα as a direct target of miR‑148a. Ectopic expression of miR‑148a significantly decreased the protein expression of ERα (P<0.01), while knockdown of miR‑148a significantly increased the ERα protein level in MCF7 cells (P<0.01). Furthermore, miR‑148a overexpression significantly inhibited the E2‑induced viability and migration of MCF7 cells (P<0.01), similar to the effect of silencing ERα. However, overexpression of ERα rescued the suppressed viability and migration caused by miR‑148a upregulation. Finally, it was found that E2 treatment led to a significant decrease in the miR‑148a level in MCF7 cells (P<0.01). These results suggest that miR‑148a can suppress the E2‑induced viability and migration of MCF7 breast cancer cells via inhibition of ERα protein expression, expanding the understanding of miR function in ERα‑positive breast cancer.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
3	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
4	Segovia-Mendoza M, González-Gonzalez ME, Barrera D, Díaz L and García-Becerra R: Efficacy and mechanism of action of the tyrosine kinase inhibitors gefitinib, lapatinib and neratinib in the treatment of HER2-positive breast cancer: Preclinical and clinical evidence. Am J Cancer Res. 5:2531–2561. 2015.PubMed/NCBI
5	Das Gupta S, Sae-Tan S, Wahler J, So JY, Bak MJ, Cheng LC, Lee MJ, Lin Y, Shih WJ, Shull JD, Safe S, et al: Dietary γ-Tocopherol rich mixture inhibits estrogen-induced mammary tumorigenesis by modulating estrogen metabolism, antioxidant response and PPARγ. Cancer Prev Res (Phila). 8:807–816. 2015. View Article : Google Scholar : PubMed/NCBI
6	Thomas C and Gustafsson JA: Estrogen receptor mutations and functional consequences for breast cancer. Trends Endocrinol Metab. 26:467–476. 2015. View Article : Google Scholar : PubMed/NCBI
7	Xu B, Lovre D and Mauvais-Jarvis F: Effect of selective estrogen receptor modulators on metabolic homeostasis. Biochimie. 124:92–97. 2016. View Article : Google Scholar : PubMed/NCBI
8	Misawa A and Inoue S: Estrogen-related receptors in breast cancer and prostate cancer. Front Endocrinol (Lausanne). 6:832015.PubMed/NCBI
9	Xiong R, Patel HK, Gutgesell LM, Zhao J, Delgado-Rivera L, Pham TN, Zhao H, Carlson K, Martin T, Katzenellenbogen JA, et al: Selective human estrogen receptor partial agonists (ShERPAs) for tamoxifen-resistant breast cancer. J Med Chem. 59:219–237. 2016. View Article : Google Scholar : PubMed/NCBI
10	Kaaks R, Lukanova A and Kurzer MS: Obesity, endogenous hormones, and endometrial cancer risk: A synthetic review. Cancer Epidemiol Biomarkers Prev. 11:1531–1543. 2002.PubMed/NCBI
11	Fan P, Maximov PY, Curpan RF, Abderrahman B and Jordan VC: The molecular, cellular and clinical consequences of targeting the estrogen receptor following estrogen deprivation therapy. Mol Cell Endocrinol. 418:245–263. 2015. View Article : Google Scholar : PubMed/NCBI
12	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
13	John B, Enright AJ, Aravin A, Tuschl T, Sander C and Marks DS: Human MicroRNA targets. PLoS Biol. 2:e3632004. View Article : Google Scholar : PubMed/NCBI
14	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
15	Boukerroucha M, Josse C, ElGuendi S, Boujemla B, Frères P, Marée R, Wenric S, Segers K, Collignon J, Jerusalem G and Bours V: Evaluation of BRCA1-related molecular features and microRNAs as prognostic factors for triple negative breast cancers. BMC Cancer. 15:7552015. View Article : Google Scholar : PubMed/NCBI
16	Kehl KL, Shen C, Litton JK, Arun B and Giordano SH: Rates of BRCA1/2 mutation testing among young survivors of breast cancer. Breast Cancer Res Treat. 155:165–173. 2016. View Article : Google Scholar : PubMed/NCBI
17	Yu J, Li Q, Xu Q, Liu L and Jiang B: MiR-148a inhibits angiogenesis by targeting ERBB3. J Biomed Res. 25:170–177. 2011. View Article : Google Scholar : PubMed/NCBI
18	Aydogdu E, Katchy A, Tsouko E, Lin CY, Haldosén LA, Helguero L and Williams C: MicroRNA-regulated gene networks during mammary cell differentiation are associated with breast cancer. Carcinogenesis. 33:1502–1511. 2012. View Article : Google Scholar : PubMed/NCBI
19	Jiang Q, He M, Ma MT, Wu HZ, Yu ZJ, Guan S, Jiang LY, Wang Y, Zheng DD, Jin F and Wei MJ: MicroRNA-148a inhibits breast cancer migration and invasion by directly targeting WNT-1. Oncol Rep. 35:1425–1432. 2016.PubMed/NCBI
20	Xue J, Chen Z, Gu X, Zhang Y and Zhang W: MicroRNA-148a inhibits migration of breast cancer cells by targeting MMP-13. Tumour Biol. 37:1581–1590. 2016. View Article : Google Scholar : PubMed/NCBI
21	Soltani S, Mokarian F and Panjehpour M: The expression of CK-19 gene in circulating tumor cells of blood samples of metastatic breast cancer women. Res Pharm Sci. 10:485–496. 2015.PubMed/NCBI
22	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. 4:e050052015. View Article : Google Scholar
23	Schröder L, Koch J, Mahner S, Kost BP, Hofmann S, Jeschke U, Haumann J, Schmedt J and Richter DU: The effects of petroselinum crispum on estrogen receptor-positive benign and malignant mammary cells (MCF12A/MCF7). Anticancer Res. 37:95–102. 2017. View Article : Google Scholar : PubMed/NCBI
24	Murphy E: Estrogen signaling and cardiovascular disease. Circ Res. 109:687–696. 2011. View Article : Google Scholar : PubMed/NCBI
25	Matthews J and Gustafsson JA: Estrogen signaling: A subtle balance between ER alpha and ER beta. Mol Interv. 3:281–292. 2003. View Article : Google Scholar : PubMed/NCBI
26	Anbalagan M and Rowan BG: Estrogen receptor alpha phosphorylation and its functional impact in human breast cancer. Mol Cell Endocrinol. 418:264–272. 2015. View Article : Google Scholar : PubMed/NCBI
27	Bondesson M, Hao R, Lin CY, Williams C and Gustafsson JÅ: Estrogen receptor signaling during vertebrate development. Biochim Biophys Acta. 1849:142–151. 2015. View Article : Google Scholar : PubMed/NCBI
28	Chan S: A review of selective estrogen receptor modulators in the treatment of breast and endometrial cancer. Semin Oncol. 29(3 Suppl 11): S129–S133. 2002. View Article : Google Scholar
29	Shang D, Li Z, Zhu Z, Chen H, Zhao L, Wang X and Chen Y: Baicalein suppresses 17-β-estradiol-induced migration, adhesion and invasion of breast cancer cells via the G protein-coupled receptor 30 signaling pathway. Oncol Rep. 33:2077–2085. 2015.PubMed/NCBI
30	Munagala R, Aqil F, Vadhanam MV and Gupta RC: MicroRNA ‘signature’ during estrogen-mediated mammary carcinogenesis and its reversal by ellagic acid intervention. Cancer Lett. 339:175–184. 2013. View Article : Google Scholar : PubMed/NCBI
31	Vilquin P, Donini CF, Villedieu M, Grisard E, Corbo L, Bachelot T, Vendrell JA and Cohen PA: MicroRNA-125b upregulation confers aromatase inhibitor resistance and is a novel marker of poor prognosis in breast cancer. Breast Cancer Res. 17:132015. View Article : Google Scholar : PubMed/NCBI
32	Yao Y, Hu J, Shen Z, Yao R, Liu S, Li Y, Cong H, Wang X, Qiu W and Yue L: MiR-200b expression in breast cancer: A prognostic marker and act on cell proliferation and apoptosis by targeting Sp1. J Cell Mol Med. 19:760–769. 2015. View Article : Google Scholar : PubMed/NCBI
33	Chen Y, Song YX and Wang ZN: The microRNA-148/152 family: Multi-faceted players. Mol Cancer. 12:432013. View Article : Google Scholar : PubMed/NCBI
34	Takahashi M, Cuatrecasas M, Balaguer F, Hur K, Toiyama Y, Castells A, Boland CR and Goel A: The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer. PLoS One. 7:e466842012. View Article : Google Scholar : PubMed/NCBI
35	Xia J, Guo X, Yan J and Deng K: The role of miR-148a in gastric cancer. J Cancer Res Clin Oncol. 140:1451–1456. 2014. View Article : Google Scholar : PubMed/NCBI
36	Li J, Song Y, Wang Y, Luo J and Yu W: MicroRNA-148a suppresses epithelial-to-mesenchymal transition by targeting ROCK1 in non-small cell lung cancer cells. Mol Cell Biochem. 380:277–282. 2013. View Article : Google Scholar : PubMed/NCBI