Long noncoding RNA MALAT1 downregulates cardiac transient outward potassium current by regulating miR-200c/HMGB1 pathway.
JOURNAL OF CELLULAR BIOCHEMISTRY(2018)
Abstract
The dysregulation of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) participates in the remodeling of electrophysiological/ion channel in cardiomyocytes during arrhythmia. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is reported to be highly expressed in myocardial ischemia-reperfusion injury and offsets cardioprotective effects of fentanyl. However, the roles of MALAT1 and its related miRNAs during arrhythmia are poorly understood. In this study, the overexpression of MALAT1 was firstly indicated in cardiomyocytes from arrhythmic model rats. After downregulation of MALAT1 by RNA interference, transient outward potassium current (Ito), peak current density, and the levels of Kv4.2 and Kv4.3 channel proteins were increased in rat cardiomyocytes. Then, miR-200c was predicted and convinced to be a direct target of MALAT1, and high-mobility group box 1 (HMGB1) was verified to be a target of miR-200c during arrhythmia. HMGB1 expression reduced by the knockdown of MALAT1 was further decreased by miR-200c overexpression. In addition, cardiac Ito, peak current density, and the levels of Kv4.2 and Kv4.3 in arrhythmic model rats were detected to be negatively correlated with the expression of HMGB1, and to be positively with miR-200c expression. Taken together, these results suggested that MALAT1 may act as a competing endogenous RNA for miR-200c to upregulate the expression of HMGB1 and downregulate cardiac Ito.
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Key words
high-mobility group box 1,long noncoding RNA,metastasis-associated lung adenocarcinoma transcript 1,miR-200c,transient outward potassium current
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