miR‑144‑3p inhibits the proliferation, migration and angiogenesis of multiple myeloma cells by targeting myocyte enhancer factor 2A

Tian,Fei; Wang,Huihan; Ma,Huanxin; Zhong,Yuan; Liao,Aijun

doi:10.3892/ijmm.2020.4670

miR‑144‑3p inhibits the proliferation, migration and angiogenesis of multiple myeloma cells by targeting myocyte enhancer factor 2A

Authors:
- Fei Tian
- Huihan Wang
- Huanxin Ma
- Yuan Zhong
- Aijun Liao
View Affiliations

Affiliations: Department of Haematology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: July 6, 2020 https://doi.org/10.3892/ijmm.2020.4670
Pages: 1155-1165
Copyright: © Tian 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

Multiple myelomas (MM) are the second most common haematological malignancy, for which no curative treatments have been reported to date. MicroRNAs (miRNAs or miRs) have recently been shown to be involved in the proliferation of MM cells. However, the molecular mechanisms through which miRNAs regulate migration and angiogenesis in MM are poorly understood. Accordingly, the present study evaluated the role of miR‑144‑3p in MM. miR‑144‑3p exhibited a lower expression in patients with MM and in MM cell lines compared with normal cells (mononuclear cells derived from bone marrow). The transfection of miR‑144‑3p into MM cells inhibited proliferation, migration and angiogenesis, and induced cell cycle arrest and apoptosis compared to the control cells. Furthermore, miR‑144‑3p suppressed the transcription and translation of the myocyte enhancer factor 2A (MEF2A) gene and disrupted the expression of vascular endothelial growth factor. The knockdown of MEF2A significantly inhibited the proliferation, migration and angiogenesis of MM cells. However, the overexpression of MEF2A reversed these effects. On the whole, the findings of the present study demonstrate that miR‑144‑3p exerts antitumour effects by downregulating MEF2A to inhibit the proliferation, migration and angiogenesis of MM cells. This suggests that the miR‑144‑3p/MEF2A interaction may prove to be a potential therapeutic target for MM.

View Figures

View References

1	Liang B, Yin JJ and Zhan XR: MiR-301a promotes cell proliferation by directly targeting TIMP2 in multiple myeloma. Int J Clin Exp Pathol. 8:9168–9174. 2015.PubMed/NCBI
2	Brigle K and Rogers B: Pathobiology and diagnosis of multiple myeloma. Semin Oncol Nurs. 33:225–236. 2017. View Article : Google Scholar : PubMed/NCBI
3	Zhao Q, Luo F, Ma J and Yu X: Bone metastasis-related Micrornas: New targets for treatment? Curr Cancer Drug Targets. 15:716–725. 2015. View Article : Google Scholar : PubMed/NCBI
4	Ribatti D and Vacca A: New insights in anti-angiogenesis in multiple myeloma. Int J Mol Sci. 19:20312018. View Article : Google Scholar :
5	D'Ario M, Griffiths-Jones S and Kim M: Small RNAs: Big impact on plant development. Trends Plant Sci. 22:1056–1068. 2017. View Article : Google Scholar : PubMed/NCBI
6	Baek D, Villén J, Shin C, Camargo FD, Gygi SP and Bartel DP: The impact of microRNAs on protein output. Nature. 455:64–71. 2008. View Article : Google Scholar : PubMed/NCBI
7	Biswas S: MicroRNAs as therapeutic agents: The future of the battle against cancer. Curr Top Med Chem. 18:2544–2554. 2018. View Article : Google Scholar : PubMed/NCBI
8	Misiewicz-Krzeminska I, Krzeminski P, Corchete LA, Quwaider D, Rojas EA, Herrero AB and Gutiérrez NC: Factors regulating microRNA expression and function in multiple myeloma. Noncoding RNA. 5:92019.
9	Lu J, Liu QH, Wang F, Tan JJ, Deng YQ, Peng XH, Liu X, Zhang B, Xu X and Li XP: Exosomal miR-9 inhibits angiogenesis by targeting MDK and regulating PDK/AKT pathway in nasopharyngeal carcinoma. J Exp Clin Cancer Res. 37:1472018. View Article : Google Scholar : PubMed/NCBI
10	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
11	He Y, Li J, Ding N, Wang X, Deng L, Xie Y, Ying Z, Liu W, Ping L, Zhang C, et al: Combination of enzastaurin and ibrutinib synergistically induces anti-tumor effects in diffuse large B cell lymphoma. J Exp Clin Cancer Res. 38:862019. View Article : Google Scholar : PubMed/NCBI
12	Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, Piedade ID, Gunsalus KC, Stoffel M and Rajewsky N: Combinatorial microRNA target predictions. Nat Genet. 37:495–500. 2005. View Article : Google Scholar : PubMed/NCBI
13	Ritchie W: MicroRNA target prediction. Methods Mol Biol. 1513:193–200. 2017. View Article : Google Scholar
14	van Iterson M, Bervoets S, de Meijer EJ, Buermans HP, Hoen PA, Menezes RX and Boer JM: Integrated analysis of microRNA and mRNA expression: Adding biological significance to microRNA target predictions. Nucleic Acids Res. 41:e1462013. View Article : Google Scholar : PubMed/NCBI
15	Li M, Linseman DA, Allen MP, Meintzer MK, Wang X, Laessig T, Wierman ME and Heidenreich KA: Myocyte enhancer factor 2A and 2D undergo phosphorylation and caspase-mediated degradation during apoptosis of rat cerebellar granule neurons. J Neurosci. 21:6544–6552. 2001. View Article : Google Scholar : PubMed/NCBI
16	Al Masri A, Price-Troska T, Chesi M, Chung TH, Kim S, Carpten J, Bergsagel PL and Fonseca R: MicroRNA expression analysis in multiple myeloma. Blood. 106:15542005. View Article : Google Scholar
17	Zhao Y, Xie Z, Lin J and Liu P: MiR-144-3p inhibits cell proliferation and induces apoptosis in multiple myeloma by targeting c-Met. Am J Transl Res. 9:2437–2446. 2017.PubMed/NCBI
18	Tianhua Y, Dianqiu L, Xuanhe Z, Zhe Z and Dongmei G: Long non-coding RNA Sox2 overlapping transcript (SOX2OT) promotes multiple myeloma progression via microRNA-143-3p/c-MET axis. J Cell Mol Med. 24:5185–5194. 2020. View Article : Google Scholar : PubMed/NCBI
19	Raimondi L, Amodio N, Di Martino MT, Altomare E, Leotta M, Caracciolo D, Gullà A, Neri A, Taverna S, D'Aquila P, et al: Targeting of multiple myeloma-related angiogenesis by miR-199a-5p mimics: In vitro and in vivo anti-tumor activity. Oncotarget. 5:3039–3054. 2014. View Article : Google Scholar : PubMed/NCBI
20	Estrella NL, Desjardins CA, Nocco SE, Clark AL, Maksimenko Y and Naya FJ: MEF2 transcription factors regulate distinct gene programs in mammalian skeletal muscle differentiation. J Biol Chem. 290:1256–1268. 2015. View Article : Google Scholar :
21	Ewen EP, Snyder CM, Wilson M, Desjardins D and Naya FJ: The Mef2A transcription factor coordinately regulates a costamere gene program in cardiac muscle. J Biol Chem. 286:29644–29653. 2011. View Article : Google Scholar : PubMed/NCBI
22	Ribatti D, Nico B, Crivellato E, Roccaro AM and Vacca A: The history of the angiogenic switch concept. Leukemia. 21:44–52. 2007. View Article : Google Scholar
23	Roccaro AM, Sacco A, Thompson B, Leleu X, Azab AK, Azab F, Runnels J, Jia X, Ngo HT, Melhem MR, et al: MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma. Blood. 113:6669–6680. 2009. View Article : Google Scholar : PubMed/NCBI
24	van de Donk NW, Lokhorst HM, Nijhuis EH, Kamphuis MM and Bloem AC: Geranylgeranylated proteins are involved in the regulation of myeloma cell growth. Clin Cancer Res. 11:429–439. 2005.PubMed/NCBI
25	Gupta N, Kumar R, Seth T, Garg B and Sharma A: Targeting of stromal versican by miR-144/199 inhibits multiple myeloma by downregulating FAK/STAT3 signalling. RNA Biol. 17:98–111. 2020. View Article : Google Scholar