Arsenic trioxide inhibits breast cancer cell growth via microRNA‑328/hERG pathway in MCF‑7 cells

Wang,Ying; Wang,Leqiu; Yin,Changhao; An,Baizhu; Hao,Yankun; Wei,Tao; Li,Li; Song,Gaochen

doi:10.3892/mmr.2015.3558

Arsenic trioxide inhibits breast cancer cell growth via microRNA‑328/hERG pathway in MCF‑7 cells

Authors:
- Ying Wang
- Leqiu Wang
- Changhao Yin
- Baizhu An
- Yankun Hao
- Tao Wei
- Li Li
- Gaochen Song
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Affiliations: Medical Functional Laboratory, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China, Department of Otolaryngology, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China, Department of Neurology, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China, Department of Anatomy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
Published online on: March 27, 2015 https://doi.org/10.3892/mmr.2015.3558
Pages: 1233-1238

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Abstract

Arsenic trioxide (As2O3) has been widely used in the treatment of acute promyelocytic leukemia and has been observed to exhibit therapeutic effects in various types of solid tumor. In a previous study by this group, it was shown that As2O3 induces the apoptosis of MCF‑7 breast cancer cells through inhibition of the human ether‑à‑go‑go‑related gene (hERG) channel. The present study was designed to further investigate the effect of As2O3 on breast cancer cells and to examine the mechanism underlying the regulation of hERG expression. The present study confirmed that As2O3 inhibited tumor growth in vivo, following MCF‑7 cell implantation into nude mice. Using computational prediction , it was identified that microRNA (miR)‑328 had a binding site in the 3'‑untranslated region of hERG mRNA. A luciferase activity assay demonstrated that hERG is a target gene of miR‑328. Further investigation using western blot analysis and reverse transcription‑quantitative polymerase chain reaction revealed that As2O3 downregulated hERG expression via upregulation of miR‑328 expression in MCF‑7 cells. In conclusion, As2O3 was observed to inhibit breast cancer cell growth, at least in part, through the miR‑328/hERG pathway.

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1	Klaassen CD: Heavy metals and heavy-metal antagonists. The Pharmacological Basis of Therapeutics. Gilman: McGraw-Hill; New York, NY: pp. 649–1672. 1996
2	Cyranoski D: Arsenic patent keeps drug for rare cancer out of reach of many. Nat Med. 13:10052007. View Article : Google Scholar : PubMed/NCBI
3	Sun HD, Ma L, Hu XC and Zhang TD: Ai-Lin I treated 32 cases of acute promyelocytic leukemia. Chin J Integr Chin W Med. 12:170–171. 1992.
4	Zhang TC, Cao EH, Li JF, Ma W and Qin JF: Induction of apoptosis and inhibition of human gastric cancer MGC-803 cell growth by arsenic trioxide. Eur J Cancer. 35:1258–1263. 1999. View Article : Google Scholar
5	Shen ZY, Shen J, Cai WJ, Hong C and Zheng MH: The alteration of mitochondria is an early event of arsenic trioxide induced apoptosis in esophageal carcinoma cells. Int J Mol Med. 5:155–158. 2000.PubMed/NCBI
6	Akao Y, Nakagawa Y and Akiyama K: Arsenic trioxide induces apoptosis in neuroblastoma cell lines through the activation of caspase 3 in vitro. FEBS Lett. 455:59–62. 1999. View Article : Google Scholar : PubMed/NCBI
7	Uslu R, Sanli UA, Sezgin C, Karabulut B, Terzioglu E, Omay SB and Goker E: Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines. Clin Cancer Res. 6:4957–4964. 2000.
8	Chow SK, Chan JY and Fung KP: Inhibition of cell proliferation and the action mechanisms of arsenic trioxide (As2O3) on human breast cancer cells. J Cell Biochem. 93:173–187. 2004. View Article : Google Scholar : PubMed/NCBI
9	Ye J, Li A, Liu Q, Wang X and Zhou J: Inhibition of mitogen-activated protein kinase kinase enhances apoptosis induced by arsenic trioxide in human breast cancer MCF-7 cells. Clin Exp Pharmacol Physiol. 32:1042–1048. 2005. View Article : Google Scholar
10	Crociani O, Guasti L, Balzi M, et al: Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells. J Biol Chem. 278:2947–2955. 2003. View Article : Google Scholar
11	Guasti L, Crociani O, Redaelli E, Pillozzi S, Polvani S, Masselli M, Mello T, Galli A, Amedei A, Wymore RS, et al: Identification of a posttranslational mechanism for the regulation of hERG1 K+ channel expression and hERG1 current density in tumor cells. Mol Cell Biol. 28:5043–5060. 2008. View Article : Google Scholar : PubMed/NCBI
12	Arcangeli A: Expression and role of hERG channels in cancer cells. Novartis Found Symp. 266:225–232. 2005.PubMed/NCBI
13	Wang Y, Zhang Y, Yang L, Cai B, Li J, Zhou Y, Yin L, Yang L, Yang BF and Lu YJ: Arsenic trioxide induces the apoptosis of human breast cancer MCF-7 cells through activation of caspase-3 and inhibition of HERG channels. Exp Ther Med. 2:481–486. 2011.PubMed/NCBI
14	Wang S, Bian C, Yang Z, Bo Y, Li J, Zeng L, Zhou H and Zhao RC: miR-145 inhibits breast cancer cell growth through RTKN. Int J Oncol. 34:1461–1466. 2009.PubMed/NCBI
15	Kato M, Paranjape T, Müller RU, Nallur S, Gillespie E, Keane K, Esquela-Kerscher A, Weidhaas JB and Slack FJ: The mir-34 microRNA is required for the DNA damage response in vivo in C. elegans and in vitro in human breast cancer cells. Oncogene. 28:2419–2424. 2009. View Article : Google Scholar : PubMed/NCBI
16	Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y and Goodall GJ: The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 10:593–601. 2008. View Article : Google Scholar : PubMed/NCBI
17	Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász AM, Wang ZC, Brock JE, Richardson AL and Weinberg RA: A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell. 137:1032–1046. 2009. View Article : Google Scholar : PubMed/NCBI
18	Wu G, Qiu XL, Zhou L, Zhu J, Chamberlin R, Lau J, Chen PL and Lee WH: Small molecule targeting the Hec1/Nek2 mitotic pathway suppresses tumor cell growth in culture and in animal. Cancer Res. 68:8393–8399. 2008. View Article : Google Scholar : PubMed/NCBI
19	Yang B, Lin H, Xiao J, Lu Y, Luo X, Li B, Zhang Y, Xu C, Bai Y, Wang H, et al: The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med. 13:486–491. 2007. View Article : Google Scholar : PubMed/NCBI
20	Lu Y, Zhang Y, Wang N, Pan Z, Gao X, Zhang F, Zhang Y, Shan H, Luo X, Bai Y, et al: MicroRNA-328 contributes to adverse electrical remodeling in atrial fibrillation. Circulation. 122:2378–2387. 2010. View Article : Google Scholar : PubMed/NCBI
21	Shan H, Zhang Y, Lu Y, Zhang Y, Pan Z, Cai B, Wang N, Li X, Feng T, Hong Y, et al: Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines. Cardiovasc Res. 83:465–472. 2009. View Article : Google Scholar : PubMed/NCBI
22	Cai B, Pan Z and Lu Y: The roles of microRNAs in heart diseases: A novel important regulator. Curr Med Chem. 17:407–411. 2010. View Article : Google Scholar
23	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. Feb 4–2015.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
24	Vahdat LT, Pruitt B, Fabian CJ, Rivera RR, Smith DA, Tan-Chiu E, Wright J, Tan AR, Dacosta NA, Chuang E, et al: Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 27:2954–2961. 2009. View Article : Google Scholar : PubMed/NCBI
25	Li H, Liu L, Guo L, et al: HERG K+ channel expression in CD34+/CD38−/CD123(high) cells and primary leukemia cells and analysis of its regulation in leukemia cells. Int J Hematol. 87:387–392. 2008. View Article : Google Scholar : PubMed/NCBI
26	Afrasiabi E, Hietamäki M, Viitanen T, Sukumaran P, Bergelin N and Törnquist K: Expression and significance of HERG (KCNH2) potassium channels in the regulation of MDA-MB-435S melanoma cell proliferation and migration. Cell Signal. 22:57–64. 2010. View Article : Google Scholar
27	Zhao J, Wei XL, Jia YS and Zheng JQ: Silencing of herg gene by shRNA inhibits SH-SY5Y cell growth in vitro and in vivo. Eur J Pharmacol. 579:50–57. 2008. View Article : Google Scholar
28	Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, et al: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65:7065–7070. 2005. View Article : Google Scholar : PubMed/NCBI
29	Wang S, Bian C, Yang Z, Bo Y, Li J, Zeng L, Zhou H and Zhao RC: miR-145 inhibits breast cancer cell growth through RTKN. Int J Oncol. 34:1461–1466. 2009.PubMed/NCBI
30	Kong W, He L, Coppola M, Guo J, Esposito NN, Coppola D and Cheng JQ: MicroRNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer. J Biol Chem. 285:17869–17879. 2010. View Article : Google Scholar : PubMed/NCBI
31	Song B, Wang C, Liu J, Wang X, Lv L, Wei L, Xie L, Zheng Y and Song X: MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression. J Exp Clin Cancer Res. 29:292010. View Article : Google Scholar : PubMed/NCBI
32	Lee EJ, Baek M, Gusev Y, Brackett DJ, Nuovo GJ and Schmittgen TD: Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors. RNA. 14:35–42. 2008. View Article : Google Scholar :
33	Wu Z, Sun L, Wang H, Yao J, Jiang C, Xu W and Yang Z: MiR-328 expression is decreased in high-grade gliomas and is associated with worse survival in primary glioblastoma. PLoS One. 7:e472702012. View Article : Google Scholar : PubMed/NCBI
34	Shah MY, Pan X, Fix LN, Farwell MA and Zhang B: 5-Fluorouracil drug alters the microRNA expression profiles in MCF-7 breast cancer cells. J Cell Physiol. 226:1868–1878. 2011. View Article : Google Scholar : PubMed/NCBI
35	Eiring AM, Harb JG, Neviani P, Garton C, Oaks JJ, Spizzo R, Liu S, Schwind S, Santhanam R, Hickey CJ, et al: miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell. 140:652–665. 2010. View Article : Google Scholar : PubMed/NCBI
36	Pan YZ, Morris ME and Yu AM: MicroRNA-328 negatively regulates the expression of breast cancer resistance protein (BCRP/ABCG2) in human cancer cells. Mol Pharmacol. 75:1374–1379. 2009. View Article : Google Scholar : PubMed/NCBI
37	Paduano F, Dattilo V, Narciso D, Bilotta A, Gaudio E, Menniti M, Agosti V, Palmieri C, Perrotti N, Fusco A, et al: Protein tyrosine phosphatase PTPRJ is negatively regulated by microRNA-328. FEBS J. 280:401–412. 2013. View Article : Google Scholar