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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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