Abstract
Myocardial infarction (MI) is one of the leading causes of high mortality worldwide. Long non-coding RNA myocardial infarction associated transcript (MIAT) and mitochondrial coupling factor 6 (CF6) aggravate MI. This study aimed to elucidate whether miR-203 interacted with MIAT and CF6 in MI. Results revealed that MIAT and CF6 expressions were upregulated and that miR-203 was downregulated in mouse myocardial tissues after MI, as well as in hypoxic mouse cardiomyocytes. The overexpression of MIAT in mouse cardiomyocytes raised CF6 expression, whereas the knockdown of MIAT had the opposite effect. Mechanistically, the luciferase reporter and RNA pull-down assays corroborated the binding between miR-203 and CF6 3′UTR and between miR-203 and MIAT. The simultaneous overexpression of miR-203 and MIAT restored the reduction of CF6 caused by miR-203 overexpression alone, and the overexpression of miR-203 diminished the percentage of infarct area and the apoptosis of cardiomyocytes in vivo. Our findings corroborate that overexpressing miR-203 alleviates MI via interacting with MIAT and CF6.
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References
Bejerano T, Etzion S, Elyagon S, Etzion Y, Cohen S (2018) Nanoparticle delivery of miRNA-21 mimic to cardiac macrophages improves myocardial remodeling after myocardial infarction. Nano Lett 18:5885–5891. https://doi.org/10.1021/acs.nanolett.8b02578
Cai B, Ma W, Ding F, Zhang L, Huang Q, Wang X, Hua B, Xu J, Li J, Bi C, Guo S, Yang F, Han Z, Li Y, Yan G, Yu Y, Bao Z, Yu M, Li F, Tian Y, Pan Z, Yang B (2018) The long noncoding RNA CAREL controls cardiac regeneration. J Am Coll Cardiol 72:534–550. https://doi.org/10.1016/j.jacc.2018.04.085
Chew C, Conos S, Unal B, Tergaonkar V (2018) Noncoding RNAs: master regulators of inflammatory signaling. Trends Mol Med 24:66–84. https://doi.org/10.1016/j.molmed.2017.11.003
Chi Y, Jin Q, Liu X, Xu L, He X, Shen Y, Zhou Q, Zhang J, Jin M (2017) miR-203 inhibits cell proliferation, invasion, and migration of non-small-cell lung cancer by downregulating RGS17. Cancer Sci 108:2366–2372. https://doi.org/10.1111/cas.13401
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (2018) Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392:1789–1858. https://doi.org/10.1016/s0140-6736(18)32279-7
Garikipati V, Verma S, Cheng Z, Liang D, Truongcao M, Cimini M, Yue Y, Huang G, Wang C, Benedict C, Tang Y, Mallaredy V, Ibetti J, Grisanti L, Schumacher S, Gao E, Rajan S, Wilusz J, Goukassian D, Houser S, Koch W, Kishore R (2019) Circular RNA CircFndc3b modulates cardiac repair after myocardial infarction via FUS/VEGF-A axis. Nat Commun 10:4317–4330. https://doi.org/10.1038/s41467-019-11777-7
He Q, Wang C, Qin J, Zhang Y, Xia D, Chen X, Guo S, Zhao X, Guo Q, Lu C (2017) Effect of miR-203 expression on myocardial fibrosis. Eur Rev Med Pharmacol Sci 21:837–842
Higuti T, Tsurumi C, Kawamura Y, Tsujita H, Osaka F, Yoshihara Y, Tani I, Tanaka K, Ichihara A (1991) Molecular cloning of cDNA for the import precursor of human coupling factor 6 of H(+)-ATP synthase in mitochondria. Biochem Biophys Res Commun 178:793–799. https://doi.org/10.1016/0006-291x(91)90178-a
Huang X, Gao Y, Qin J, Lu S (2018) lncRNA MIAT promotes proliferation and invasion of HCC cells via sponging miR-214. Am J Physiol Gastrointest Liver Physiol 314:G559–G565. https://doi.org/10.1152/ajpgi.00242.2017
Kaikkonen M, Adelman K (2018) Emerging roles of non-coding RNA transcription. Trends Biochem Sci 43:654–667. https://doi.org/10.1016/j.tibs.2018.06.002
Li P, Guo Y, Bledsoe G, Yang Z, Chao L, Chao J (2016) Kallistatin induces breast cancer cell apoptosis and autophagy by modulating Wnt signaling and microRNA synthesis. Exp Cell Res 340:305–314. https://doi.org/10.1016/j.yexcr.2016.01.004
Liang H, Pan Z, Zhao X, Liu L, Sun J, Su X, Xu C, Zhou Y, Zhao D, Xu B, Li X, Yang B, Lu Y, Shan H (2018) LncRNA PFL contributes to cardiac fibrosis by acting as a competing endogenous RNA of let-7d. Theranostics 8:1180–1194. https://doi.org/10.7150/thno.20846
Liang H, Su X, Wu Q, Shan H, Lv L, Yu T, Zhao X, Sun J, Yang R, Zhang L, Yan H, Zhou Y, Li X, Du Z, Shan H (2019) LncRNA 2810403D21Rik/Mirf promotes ischemic myocardial injury by regulating autophagy through targeting Mir26a. Autophagy 16:1077–1091. https://doi.org/10.1080/15548627.2019.1659610
Liao J, He Q, Li M, Chen Y, Liu Y, Wang J (2016) LncRNA MIAT: myocardial infarction associated and more. Gene 578:158–161. https://doi.org/10.1016/j.gene.2015.12.032
Liu C, Zhang Y, Li R, Zhou L, An T, Zhang R, Zhai M, Huang Y, Yan K, Dong Y, Ponnusamy M, Shan C, Xu S, Wang Q, Zhang Y, Zhang J, Wang K (2018) LncRNA CAIF inhibits autophagy and attenuates myocardial infarction by blocking p53-mediated myocardin transcription. Nat Commun 9:29–43. https://doi.org/10.1038/s41467-017-02280-y
Ma M, Pei Y, Wang X, Feng J, Zhang Y, Gao M (2019) LncRNA XIST mediates bovine mammary epithelial cell inflammatory response via NF-κB/NLRP3 inflammasome pathway. Cell Prolif 52:e12525. https://doi.org/10.1111/cpr.12525
Magnani S, Roberto S, Sainas G, Milia R, Palazzolo G, Cugusi L, Pinna V, Doneddu A, Kakhak S, Tocco F, Mercuro G, Crisafulli A (2018) Metaboreflex-mediated hemodynamic abnormalities in individuals with coronary artery disease without overt signs or symptoms of heart failure. Am J Physiol Heart Circ Physiol 314:H452–H463. https://doi.org/10.1152/ajpheart.00436.2017
Morrow D (2020) The fourth universal definition of myocardial infarction and the emerging importance of myocardial injury. Circulation 141:172–175. https://doi.org/10.1161/circulationaha.119.044125
Ohnishi Y, Tanaka T, Yamada R, Suematsu K, Minami M, Fujii K, Hoki N, Kodama K, Nagata S, Hayashi T, Kinoshita N, Sato H, Sato H, Kuzuya T, Takeda H, Hori M, Nakamura Y (2000) Identification of 187 single nucleotide polymorphisms (SNPs) among 41 candidate genes for ischemic heart disease in the Japanese population. Hum Genet 106:288–292. https://doi.org/10.1007/s004390051039
Osanai T, Nakamura M, Sasaki S, Tomita H, Saitoh M, Osawa H, Yamabe H, Murakami S, Magota K, Okumura K (2003) Plasma concentration of coupling factor 6 and cardiovascular events in patients with end-stage renal disease. Kidney Int 64:2291–2297. https://doi.org/10.1046/j.1523-1755.2003.00334.x
Osanai T, Okada S, Sirato K, Nakano T, Saitoh M, Magota K, Okumura K (2001) Mitochondrial coupling factor 6 is present on the surface of human vascular endothelial cells and is released by shear stress. Circulation 104:3132–3136. https://doi.org/10.1161/hc5001.100832
Shen J, Zhang J, Xiao M, Yang J, Zhang N (2018) miR-203 suppresses bladder cancer cell growth and targets Twist1. Oncol Res 26:1155–1165. https://doi.org/10.3727/096504017x15041934685237
Tan H, Qi J, Fan B, Zhang J, Su F, Wang H (2018) MicroRNA-24-3p attenuates myocardial ischemia/reperfusion injury by suppressing RIPK1 expression in mice. Cell Physiol Biochem 51:46–62. https://doi.org/10.1159/000495161
Topol E, Ellis S, Califf R, George B, Stump D, Bates E, Nabel E, Walton J, Candela R, Lee K, Kline E, Pitt B (1989) Combined tissue-type plasminogen activator and prostacyclin therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 4 Study Group. J Am Coll Cardiol 14:877–884. https://doi.org/10.1016/0735-1097(89)90458-0
Wang J, Ke L, Jiang X, Zhang C (2018) A review of microRNAs related to the occurrence, diagnosis, and prognosis of non-small cell lung cancer. Clin Surg Res Commun 2:1–9. https://doi.org/10.31491/CSRC.2018.9.017
Yang X, Li X, Lin Q, Xu Q (2019) Up-regulation of microRNA-203 inhibits myocardial fibrosis and oxidative stress in mice with diabetic cardiomyopathy through the inhibition of PI3K/Akt signaling pathway via PIK3CA. Gene 715:143995. https://doi.org/10.1016/j.gene.2019.143995
Ye Z, Yang S, Xia Y, Hu R, Chen S, Li B, Chen S, Luo X, Mao L, Li Y, Jin H, Qin C, Hu B (2019) LncRNA MIAT sponges miR-149-5p to inhibit efferocytosis in advanced atherosclerosis through CD47 upregulation. Cell Death Dis 10:138–151. https://doi.org/10.1038/s41419-019-1409-4
Hui Y, Huang Y, Ding X, Wang L (2019) MicroRNA-152 suppresses cell proliferation and tumor growth of bladder cancer by targeting KLF5 and MKK7. Aging Pathobiol Therapeutics 1:10–16. https://doi.org/10.31491/APT.2019.12.003
Yu S, Dong B, Fang Z, Hu X, Tang L, Zhou S (2018) Knockdown of lncRNA AK139328 alleviates myocardial ischaemia/reperfusion injury in diabetic mice via modulating miR-204-3p and inhibiting autophagy. J Cell Mol Med 22:4886–4898. https://doi.org/10.1111/jcmm.13754
Zhang J, Pan J, Yang M, Jin X, Feng J, Wang A, Chen Z (2019) Up-regulating microRNA-203 alleviates myocardial remodeling and cell apoptosis through down-regulating PTP1B in rats with myocardial infarction. J Cardiovasc Pharmacol 74:474–481. https://doi.org/10.1097/fjc.0000000000000733
Zhou X, Zhang W, Jin M, Chen J, Xu W, Kong X (2017) lncRNA MIAT functions as a competing endogenous RNA to upregulate DAPK2 by sponging miR-22-3p in diabetic cardiomyopathy. Cell Death Dis 8:e2929. https://doi.org/10.1038/cddis.2017.321
Zhu K, Zhang C, Ma X, Hu J, Cai T, Zhang L (2019) Analyzing the interactions of mRNAs and ncRNAs to predict competing endogenous RNA networks in osteosarcoma chemo-resistance. Mol Ther 27:518–530. https://doi.org/10.1016/j.ymthe.2019.01.001
Zhu L, Tian T, Wang J, He J, Chen T, Pan M, Xu L, Zhang H, Qiu X, Li C, Wang K, Shen H, Zhang G, Bai Y (2018) Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction. Theranostics 8:6163–6177. https://doi.org/10.7150/thno.28021
Zierau O, Helle J, Schadyew S, Morgenroth Y, Bentler M, Hennig A, Chittur S, Tenniswood M, Kretzschmar G (2018) Role of miR-203 in estrogen receptor-mediated signaling in the rat uterus and endometrial carcinoma. Journal of cellular biochemistry 119:5359–5372. https://doi.org/10.1002/jcb.26675
Acknowledgments
This study was supported by the National Natural Science Foundation of China (grant no. 81870253), the Shandong Taishan Scholarship, and the Academic promotion program of Shandong First Medical University (grant no. 2019QL012).
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Fan Wang and Renliang Yu contributed equally to this work.
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12272_2021_1324_MOESM1_ESM.tif
Supplementary file1 Fig. S1. The effect of Adv-CF6 and Adv-sh-CF6 on the expressions of MIAT and CF6 in MI myocardial tissues. One day after the LAD ligation, the mice were injected with Adv-CF6 or Adv-sh-CF6 (8×109 pfu/mL, 2.5 μL) via myocardial tissues (n = 6 in each group). The expressions of MIAT and CF6 mRNA were tested using the qRT-PCR. Three independent experiments. The difference among three or more groups was analyzed using analysis of variance (ANOVA) followed by the Tukey post hoc test. ***p < 0.001 vs Adv-CF6 control (OE-NC) or Adv-sh-CF6 control (sh-NC). (TIF 281 kb)
12272_2021_1324_MOESM2_ESM.tif
Supplementary file2 Fig. S2. The effect of Adv-miR-203 and Adv-MIAT on myocardial expressions of miR-203 and MIAT. Mice were injected with Adv-miR-203 or Adv-MIAT (8×109 pfu/mL, 2.5 μL) via myocardial tissues (n = 6 in each group). The control group was injected with the same volume of saline. The expressions of miR-203 (A) and MIAT (B) were tested using the qRT-PCR. Three independent experiments. The difference among three or more groups was analyzed using analysis of variance (ANOVA) followed by the Tukey post hoc test. ***p < 0.001 vs Adv-miR-203 control (miR-NC) or Adv-MIAT control (OE-NC). (TIF 105 kb)
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Wang, F., Yu, R., Wen, S. et al. Overexpressing microRNA-203 alleviates myocardial infarction via interacting with long non-coding RNA MIAT and mitochondrial coupling factor 6. Arch. Pharm. Res. 44, 525–535 (2021). https://doi.org/10.1007/s12272-021-01324-8
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DOI: https://doi.org/10.1007/s12272-021-01324-8