microRNA-208a in an early stage myocardial infarction rat model and the effect on cAMP-PKA signaling pathway

Feng,Gao; Yan,Zhang; Li,Chuanchuan; Hou,Yuemei

doi:10.3892/mmr.2016.5402

microRNA-208a in an early stage myocardial infarction rat model and the effect on cAMP-PKA signaling pathway

Authors:
- Gao Feng
- Zhang Yan
- Chuanchuan Li
- Yuemei Hou
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Affiliations: The Third Clinical Medical College of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Fuzhou First Hospital Affiliated to Fujian Medical University, Fuzhou, Fujian 350000, P.R. China, Fengxian Hospital Affiliated to Southern Medical University, Shanghai 201400, P.R. China
Published online on: June 14, 2016 https://doi.org/10.3892/mmr.2016.5402
Pages: 1631-1635
Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The expression level of microRNA-208a (miR-208a) in a rat model with myocardial infarction and the effect of cAMP-PKA signaling pathway in early stage of myocardial infarction in rats were investigated. The early myocardial infarction model was established in 12 male Sprague-Dawley rats by ligation of the anterior descending coronary artery, and 12 rats were selected as the control group (sham operation group). Reverse-transcription quantitative PCR was conducted to detect the expression levels of miR-208a in the myocardium of and the expression levels of miR‑208a in the serum of rats in the two groups. Western blot analysis was used to evaluate the expression levels of cAMP-PKA protein in the rat tissues in the two groups. After stimulating high levels of miR‑208a expression in human myocardial cells (HCM), western blot analysis was used to detect the cAMP-PKA protein levels. The expression levels of miR‑208a in myocardial tissues in rats with myocardial infarction were significantly higher than those in the control group, and the difference was statistically significant (P<0.05). The expression levels of miR‑208a in the early stage of myocardial infarction rats were also significantly higher than those in the control group, and the difference was statistically significant (P<0.05). The level of cAMP-PKA protein in myocardial tissue in rats with chronic myocardial infarction was also significantly higher. Transfection of human myocardial cells with miR‑208a analogue significantly increased the cAMP-PKA protein levels in human myocardial cells. In conclusion, the overexpression of miR-208a in myocardial infarction tissue and the high levels of this miRNA in the serum, may be involved in the process of myocardial infarction by influencing the cAMP-PKA signaling pathway in myocardial cells.

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1	Li Z, Ying X, Chen H, Ye P, Shen Y, Pan W and Zhang L: MicroRNA-194 inhibits the epithelial-mesenchymal transition in gastric cancer cells by targeting FoxM1. Dig Dis Sci. 59:2145–2152. 2014. View Article : Google Scholar : PubMed/NCBI
2	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
3	Cheng Y, Liu X, Yang J, Lin Y, Xu DZ, Lu Q, Deitch EA, Huo Y, Delphin ES and Zhang C: MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res. 105:158–166. 2009. View Article : Google Scholar : PubMed/NCBI
4	Suárez Y, Fernández-Hernando C, Pober JS and Sessa WC: Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res. 100:1164–1173. 2007. View Article : Google Scholar : PubMed/NCBI
5	Callis TE, Pandya K, Seok HY, Tang RH, Tatsuguchi M, Huang ZP, Chen JF, Deng Z, Gunn B, Shumate J, et al: MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest. 119:2772–2786. 2009. View Article : Google Scholar : PubMed/NCBI
6	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
7	Newby AC: Metalloproteinases promote plaque rupture and myocardial infarction: A persuasive concept waiting for clinical translation. Matrix Biol. 44–46:157–66. 2015. View Article : Google Scholar
8	Zhang Y, Zhou ZG, Wang L, Zhang P, Wang MJ, Cui CF, Guan JT, Chen KL and Zhan L: Clinicopathological significance of microRNA-21 and miR-125 expression in colorectal cancer. Zhonghua Wei Chang Wai Ke Za Zhi. 12:623–626. 2009.In Chinese. PubMed/NCBI
9	Du J, Yang S, An D, Hu F, Yuan W, Zhai C and Zhu T: BMP-6 inhibits microRNA-21 expression in breast cancer through repressing deltaEF1 and AP-1. Cell Res. 19:487–496. 2009. View Article : Google Scholar : PubMed/NCBI
10	Zhang JG, Wang JJ, Zhao F, Liu Q, Jiang K and Yang GH: MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin Chim Acta. 411:846–852. 2010. View Article : Google Scholar : PubMed/NCBI
11	Bae HJ, Noh JH, Kim JK, Eun JW, Jung KH, Kim MG, Chang YG, Shen Q, Kim SJ, Park WS, et al: MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma. Oncogene. 33:2557–2567. 2014. View Article : Google Scholar
12	Fan DN, Tsang FH, Tam AH, Au SL, Wong CC, Wei L, Lee JM, He X, Ng IO and Wong CM: Histone lysine methyltransferase, suppressor of variegation 3–9 homolog 1, promotes hepatocellular carcinoma progression and is negatively regulated by microRNA-125b. Hepatology. 57:637–647. 2013. View Article : Google Scholar
13	Zhu H and Fan GC: Role of microRNAs in the reperfused myocardium towards post-infarct remodelling. Cardiovasc Res. 94:284–292. 2012. View Article : Google Scholar :
14	Rane S, He M, Sayed D, Vashistha H, Malhotra A, Sadoshima J, Vatner DE, Vatner SF and Abdellatif M: Downregulation of miR-199a derepresses hypoxia-inducible factor-1alpha and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ Res. 104:879–886. 2009. View Article : Google Scholar : PubMed/NCBI
15	Raghunandan R and Ingram VM: Hyperphosphorylation of the cytoskeletal protein Tau by the MAP-kinase PK40erk2: regulation by prior phosphorylation with cAMP-dependent protein kinase A. Biochem Biophys Res Commun. 215:1056–1066. 1995. View Article : Google Scholar : PubMed/NCBI
16	Fantidis P: The role of intracellular 3′5′-cyclic adenosine mono-phosphate (cAMP) in atherosclerosis. Curr Vasc Pharmacol. 8:464–472. 2010. View Article : Google Scholar