MicroRNA-384 inhibits the progression of breast cancer by targeting ACVR1

Wang,Yongxia; Zhang,Zheying; Wang,Jianqiang

doi:10.3892/or.2018.6385

MicroRNA-384 inhibits the progression of breast cancer by targeting ACVR1

Authors:
- Yongxia Wang
- Zheying Zhang
- Jianqiang Wang
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Affiliations: Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
Published online on: April 20, 2018 https://doi.org/10.3892/or.2018.6385
Pages: 2563-2574
Copyright: © Wang 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 leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancer cases and has a poorer prognosis than other subtypes. Moreover, the treatment for breast cancer, especially for TNBC, remains unsatisfactory. Therefore, novel therapies are urgently needed. Microribonucleic acids (miRNAs) are a class of biomarkers and therapeutic targets in many types of cancers. In the present study, the expression of miR-384 was explored in GSE58606 and in fresh breast cancer tissues by qPCR. The results showed that miR-384 was decreased in breast cancer, especially in TNBC. The results of MTT, colony formation, soft agar, Transwell migration, wound healing and the tumorigenesis assay demonstranted that overexpression of miR-384 inhibited the proliferation and migration of breast cancer in vitro and in vivo; knockdown of miR-384 enhanced the proliferation and migration of breast cancer. In addition, luciferase assay showed that Activin A receptor type 1 (ACVR1) was a direct target of miR-384 and is involved in the inhibitory effects of miR-384 on breast cancer progression. Furthermore, this study indicated that ACVR1 activated the Wnt/β-catenin signaling pathway in breast cancer. In conclusion, our findings revealed functional and mechanistic links between miR-384 and ACVR1 in the progression of breast cancer. miR-384 not only plays an important role in the progression of breast cancer, but has promise as a potential therapeutic target for breast cancer especially for TNBC.

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1	Denny L, de Sanjose S, Mutebi M, Anderson BO, Kim J, Jeronimo J, Herrero R, Yeates K, Ginsburg O and Sankaranarayanan R: Interventions to close the divide for women with breast and cervical cancer between low-income and middle-income countries and high-income countries. Lancet. 389:861–870. 2017. View Article : Google Scholar : PubMed/NCBI
2	Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y and Pietenpol JA: Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 121:2750–2767. 2011. View Article : Google Scholar : PubMed/NCBI
3	Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SA, Savage MI, Osborne CK, Hilsenbeck SG, Chang JC, et al: Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 21:1688–1698. 2015. View Article : Google Scholar : PubMed/NCBI
4	Cappato S, Tonachini L, Giacopelli F, Tirone M, Galietta LJ, Sormani M, Giovenzana A, Spinelli AE, Canciani B, Brunelli S, et al: High-throughput screening for modulators of ACVR1 transcription: Discovery of potential therapeutics for fibrodysplasia ossificans progressiva. Dis Model Mech. 9:685–696. 2016. View Article : Google Scholar : PubMed/NCBI
5	Wang K, Sun X, Feng HL, Fei C and Zhang Y: DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway. Oncol Rep. 37:879–886. 2017. View Article : Google Scholar : PubMed/NCBI
6	Li L, Liu Y, Guo Y, Liu B, Zhao Y, Li P, Song F, Zheng H, Yu J, Song T, et al: Regulatory MiR-148a-ACVR1/BMP circuit defines a cancer stem cell-like aggressive subtype of hepatocellular carcinoma. Hepatology. 61:574–584. 2015. View Article : Google Scholar : PubMed/NCBI
7	Lujambio A and Lowe SW: The microcosmos of cancer. Nature. 482:347–355. 2012. View Article : Google Scholar : PubMed/NCBI
8	Pencheva N and Tavazoie SF: Control of metastatic progression by microRNA regulatory networks. Nat Cell Biol. 15:546–554. 2013. View Article : Google Scholar : PubMed/NCBI
9	Pencheva N, Tran H, Buss C, Huh D, Drobnjak M, Busam K and Tavazoie SF: Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell. 151:1068–1082. 2012. View Article : Google Scholar : PubMed/NCBI
10	Jena MK: MicroRNAs in the development and neoplasia of the mammary gland. F1000 Res. 6:10182017. View Article : Google Scholar
11	Rodriguez-Barrueco R, Nekritz EA, Bertucci F, Yu J, Sanchez-Garcia F, Zeleke TZ, Gorbatenko A, Birnbaum D, Ezhkova E, Cordon-Cardo C, et al: miR-424(322)/503 is a breast cancer tumor suppressor whose loss promotes resistance to chemotherapy. Genes Dev. 31:553–566. 2017. View Article : Google Scholar : PubMed/NCBI
12	Shen Y, Ye YF, Ruan LW, Bao L, Wu MW and Zhou Y: Inhibition of miR-660-5p expression suppresses tumor development and metastasis in human breast cancer. Genet Mol Res. 16:2017. View Article : Google Scholar
13	Eom S, Kim Y, Park D, Lee H, Lee YS, Choe J, Kim YM and Jeoung D: Histone deacetylase-3 mediates positive feedback relationship between anaphylaxis and tumor metastasis. J Biol Chem. 289:12126–12144. 2014. View Article : Google Scholar : PubMed/NCBI
14	Lai YY, Shen F, Cai WS, Chen JW, Feng JH, Cao J, Xiao HQ, Zhu GH and Xu B: MiR-384 regulated IRS1 expression and suppressed cell proliferation of human hepatocellular carcinoma. Tumour Biol. 37:14165–14171. 2016. View Article : Google Scholar : PubMed/NCBI
15	Zheng J, Liu X, Wang P, Xue Y, Ma J, Qu C and Liu Y: CRNDE promotes malignant progression of glioma by attenuating miR-384/PIWIL4/STAT3 axis. Mol Ther. 24:1199–1215. 2016. View Article : Google Scholar : PubMed/NCBI
16	Wang YX, Chen YR, Liu SS, Ye YP, Jiao HL, Wang SY, Xiao ZY, Wei WT, Qiu JF, Liang L, et al: MiR-384 inhibits human colorectal cancer metastasis by targeting KRAS and CDC42. Oncotarget. 7:84826–84838. 2016.PubMed/NCBI
17	Matamala N, Vargas MT, González-Cámpora R, Miñambres R, Arias JI, Menéndez P, Andrés-León E, Gómez-López G, Yanowsky K, Calvete-Candenas J, et al: Tumor microRNA expression profiling identifies circulating microRNAs for early breast cancer detection. Clin Chem. 61:1098–1106. 2015. View Article : Google Scholar : PubMed/NCBI
18	Ye YP, Wu P, Gu CC, Deng DL, Jiao HL, Li TT, Wang SY, Wang YX, Xiao ZY, Wei WT, et al: miR-450b-5p induced by oncogenic KRAS is required for colorectal cancer progression. Oncotarget. 7:61312–61324. 2016. View Article : Google Scholar : PubMed/NCBI
19	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
20	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
21	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
22	Shi C, Yang Y, Xia Y, Okugawa Y, Yang J, Liang Y, Chen H, Zhang P, Wang F, Han H, et al: Novel evidence for an oncogenic role of microRNA-21 in colitis-associated colorectal cancer. Gut. 65:1470–1481. 2016. View Article : Google Scholar : PubMed/NCBI
23	Liu M, Huang F, Zhang D, Ju J, Wu XB, Wang Y, Wang Y, Wu Y, Nie M, Li Z, et al: Heterochromatin protein HP1γ promotes colorectal cancer progression and is regulated by miR-30a. Cancer Res. 75:4593–4604. 2015. View Article : Google Scholar : PubMed/NCBI
24	Loo JM, Scherl A, Nguyen A, Man FY, Weinberg E, Zeng Z, Saltz L, Paty PB and Tavazoie SF: Extracellular metabolic energetics can promote cancer progression. Cell. 160:393–406. 2015. View Article : Google Scholar : PubMed/NCBI
25	Massagué J: TGF-beta signal transduction. Annu Rev Biochem. 67:753–791. 1998. View Article : Google Scholar : PubMed/NCBI
26	Kamiya N, Kaartinen VM and Mishina Y: Loss-of-function of ACVR1 in osteoblasts increases bone mass and activates canonical Wnt signaling through suppression of Wnt inhibitors SOST and DKK1. Biochem Biophys Res Commun. 414:326–330. 2011. View Article : Google Scholar : PubMed/NCBI
27	Slattery ML, John EM, Torres-Mejia G, Herrick JS, Giuliano AR, Baumgartner KB, Hines LM and Wolff RK: Genetic variation in bone morphogenetic proteins and breast cancer risk in hispanic and non-hispanic white women: The breast cancer health disparities study. Int J Cancer. 132:2928–2939. 2013. View Article : Google Scholar : PubMed/NCBI
28	Kawano Y and Kypta R: Secreted antagonists of the Wnt signalling pathway. J Cell Sci. 116:2627–2634. 2003. View Article : Google Scholar : PubMed/NCBI
29	Reed KR, Athineos D, Meniel VS, Wilkins JA, Ridgway RA, Burke ZD, Muncan V, Clarke AR and Sansom OJ: B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver. Proc Natl Acad Sci USA. 105:18919–18923. 2008. View Article : Google Scholar : PubMed/NCBI
30	Arce L, Yokoyama NN and Waterman ML: Diversity of LEF/TCF action in development and disease. Oncogene. 25:7492–7504. 2006. View Article : Google Scholar : PubMed/NCBI
31	Lu FI, Sun YH, Wei CY, Thisse C and Thisse B: Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/β-catenin pathway. Nat Commun. 5:53682014. View Article : Google Scholar : PubMed/NCBI
32	Yamada N, Noguchi S, Mori T, Naoe T, Maruo K and Akao Y: Tumor-suppressive microRNA-145 targets catenin δ-1 to regulate Wnt/β-catenin signaling in human colon cancer cells. Cancer Lett. 335:332–342. 2013. View Article : Google Scholar : PubMed/NCBI
33	Zhou AD, Diao LT, Xu H, Xiao ZD, Li JH, Zhou H and Qu LH: β-Catenin/LEF1 transactivates the microRNA-371-373 cluster that modulates the Wnt/β-catenin-signaling pathway. Oncogene. 31:2968–2978. 2012. View Article : Google Scholar : PubMed/NCBI
34	Ji S, Ye G, Zhang J, Wang L, Wang T, Wang Z, Zhang T, Wang G, Guo Z, Luo Y, et al: miR-574-5p negatively regulates Qki6/7 to impact β-catenin/Wnt signalling and the development of colorectal cancer. Gut. 62:716–726. 2013. View Article : Google Scholar : PubMed/NCBI
35	Cai J, Guan H, Fang L, Yang Y, Zhu X, Yuan J, Wu J and Li M: MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis. J Clin Invest. 123:566–579. 2013.PubMed/NCBI
36	Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, Huber M, Hohl D, Cano A, Birchmeier W and Huelsken J: Cutaneous cancer stem cell maintenance is dependent on betacatenin signalling. Nature. 452:650–653. 2008. View Article : Google Scholar : PubMed/NCBI