Upregulation of microRNA-143 reverses drug resistance in human breast cancer cells via inhibition of cytokine-induced apoptosis inhibitor 1

Wang,Jing‑Hao; Wang,Xiu‑Wen; Qu,Di; Sun,Ji‑Wen; Guo,Fei‑Xiao; Lu,Dan

doi:10.3892/ol.2017.6078

Upregulation of microRNA-143 reverses drug resistance in human breast cancer cells via inhibition of cytokine-induced apoptosis inhibitor 1

Authors:
- Jing‑Hao Wang
- Xiu‑Wen Wang
- Di Qu
- Ji‑Wen Sun
- Fei‑Xiao Guo
- Dan Lu
View Affiliations

Affiliations: Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: April 24, 2017 https://doi.org/10.3892/ol.2017.6078
Pages: 4695-4700
Copyright: © Wang 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

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1), originally termed anamorsin, is an anti‑apoptotic molecule that acts as a downstream effector of the receptor tyrosine kinase‑Ras signaling pathway. Overexpression of CIAPIN1 contributes to multidrug resistance (MDR) and microRNA (miR)‑143 is typically considered a tumor suppressor in breast cancer. The present study aimed to evaluate the therapeutic potential of miR‑143 as a treatment for drug‑resistant breast cancer via the downregulation of CIAPIN1 in vitro. The expression levels of miR‑143 were measured using quantitative polymerase chain reaction and the expression levels of CIAPIN1 were detected via western blot analysis. Bioinformatic analyses was additionally conducted to search for miR‑143, which may potentially target CIAPIN1. Luciferase reporter plasmids were created and used to verify direct targeting. In addition, Taxol‑induced drug‑resistant (TDR) breast cancer cell proliferation was evaluated using the Cell Counting Kit‑8 assay in vitro. The present study identified an inverse association between miR‑143 and CIAPIN1 protein expression levels in breast cancer MCF‑7, MDA‑MB‑231 and MDA‑MB‑453 TDR cells. Specific targeting sites for miR‑143 in the 3'‑untranslated region of the CIAPIN1 gene were identified, which exhibit the ability to regulate CIAPIN1 expression. It was revealed that the repression of CIAPIN1 via miR‑143 suppressed the proliferation of breast cancer TDR cells. The findings of the present study verified the role of miR‑143 as a tumor suppressor in breast cancer MDR via inhibition of CIAPIN1 translation.

View Figures

View References

1	Guo P, Huang ZL, Yu P and Li K: Trends in cancer mortality in China: An update. Ann Oncol. 23:2755–2762. 2012. View Article : Google Scholar : PubMed/NCBI
2	Seruga B, Hertz PC, Le LW and Tannock IF: Global drug development in cancer: A cross-sectional study of clinical trial registries. Ann Oncol. 21:895–900. 2010. View Article : Google Scholar : PubMed/NCBI
3	Marquette C and Nabell L: Chemotherapy-resistant metastatic breast cancer. Curr Treat Options Oncol. 13:263–275. 2012. View Article : Google Scholar : PubMed/NCBI
4	Gonzalez-Angulo AM, Morales-Vasquez F and Hortobagyi GN: Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 608:1–22. 2007. View Article : Google Scholar : PubMed/NCBI
5	Kuo MT: Roles of multidrug resistance genes in breast cancer chemoresistance. Adv Exp Med Biol. 608:23–30. 2007. View Article : Google Scholar : PubMed/NCBI
6	Cascorbi I: Role of pharmacogenetics of ATP-binding cassette transporters in the pharmacokinetics of drugs. Pharmacol Ther. 112:457–473. 2006. View Article : Google Scholar : PubMed/NCBI
7	Shibayama H, Takai E, Matsumura I, Kouno M, Morii E, Kitamura Y, Takeda J and Kanakura Y: Identification of a cytokine-induced antiapoptotic molecule anamorsin essential for definitive hematopoiesis. J Exp Med. 199:581–592. 2004. View Article : Google Scholar : PubMed/NCBI
8	Hao Z, Li X, Qiao T, Du R, Hong L and Fan D: CIAPIN1 confers multidrug resistance by upregulating the expression of MDR-1 and MRP-1 in gastric cancer cells. Cancer Biol Ther. 5:261–266. 2006. View Article : Google Scholar : PubMed/NCBI
9	Li X, Fan R, Zou X, Hong L, Gao L, Jin H, Du R, He L, Xia L and Fan D: Reversal of multidrug resistance of gastric cancer cells by down-regulation of CIAPIN1 with CIAPIN1 siRNA. Mol Biol (Mosk). 42:102–109. 2008.(In Russian). View Article : Google Scholar : PubMed/NCBI
10	Li X, Hong L, Zhao Y, Jin H, Fan R, Du R, Xia L, Luo G and Fan D: A new apoptosis inhibitor, CIAPIN1 (cytokine-induced apoptosis inhibitor1), mediates multidrug resistance in leukemia cells by regulating MDR-1, Bcl-2, and Bax. Biochem Cell Biol. 85:741–750. 2007. View Article : Google Scholar : PubMed/NCBI
11	Lu D, Xiao Z, Wang W, Xu Y, Gao S, Deng L, He W, Yang Y, Guo X and Wang X: Down regulation of CIAPIN1 reverses multidrug resistance in human breast cancer cells by inhibiting MDR1. Molecules. 17:7595–7611. 2012. View Article : Google Scholar : PubMed/NCBI
12	Li X, Wu K and Fan D: CIAPIN1 as a therapeutic target in cancer. Expert Opin Ther Targets. 14:603–610. 2010. View Article : Google Scholar : PubMed/NCBI
13	Andorfer CA, Necela BM, Thompson EA and Perez EA: MicroRNA signatures: Clinical biomarkers for the diagnosis and treatment of breast cancer. Trends Mol Med. 17:313–319. 2011. View Article : Google Scholar : PubMed/NCBI
14	Shi M and Guo N: MicroRNA expression and its implications for the diagnosis and therapeutic strategies of breast cancer. Cancer Treat Rev. 35:328–334. 2009. View Article : Google Scholar : PubMed/NCBI
15	Jiang S, Zhang LF, Zhang HW, Hu S, Lu MH, Liang S, Li B, Li Y, Li D, Wang ED and Liu MF: A novel miR-155/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells. EMBO J. 31:1985–1998. 2012. View Article : Google Scholar : PubMed/NCBI
16	Yan X, Chen X, Liang H, Deng T, Chen W, Zhang S, Liu M, Gao X, Liu Y, Zhao C, et al: miR-143 and miR-145 synergistically regulate ERBB3 to suppress cell proliferation and invasion in breast cancer. Mol Cancer. 13:2202014. View Article : Google Scholar : PubMed/NCBI
17	Livak and Schmittgen: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Egerton N: Ixabepilone (ixempra), a therapeutic option for locally advanced or metastatic breast cancer. P T. 33:523–531. 2008.PubMed/NCBI
19	Wang XM, Gao SJ, Guo XF, Sun WJ, Yan ZQ, Wang WX, Xu YQ and Lu D: CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo. Braz J Med Biol Res. 47:273–278. 2014. View Article : Google Scholar : PubMed/NCBI
20	Zhang ZQ, Meng H, Wang N, Liang LN, Liu LN, Lu SM and Luan Y: Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma. Diagn Pathol. 9:1352014. View Article : Google Scholar : PubMed/NCBI
21	Zhuang M, Shi Q, Zhang X, Ding Y, Shan L, Shan X, Qian J, Zhou X, Huang Z, Zhu W, et al: Involvement of miR-143 in cisplatin resistance of gastric cancer cells via targeting IGF1R and BCL2. Tumour Biol. 36:2737–2745. 2015. View Article : Google Scholar : PubMed/NCBI