MicroRNA-1976 regulates degeneration of the sinoatrial node by targeting Ca(v)1.2 and Ca(v)1.3 ion channels

	MicroRNA-1976 regulates degeneration of the sinoatrial node by targeting Ca(v)1.2 and Ca(v)1.3 ion channels
	Zhang, J; Wei, FY; Ding, LQ; Wang, LL; Zhang, X; Yu, L; Liu, R; Kuang, XH; Jiao, BW; Yang, B; Fan, J
	2019
发表期刊	JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
ISSN	0022-2828
卷号	134 页码:74-85
摘要	Sick sinus syndrome (SSS) is primarily a disease of the elderly, and age-dependent decrease in Ca(v)1.2 and Ca(v)1.3 Ca2+ channels within the sinus node has been shown to play an important role in sinoatrial node (SAN) degeneration; however, posttranscriptional mechanisms regulating decrease in Ca(v)1.2 and Ca(v)1.3 Ca2+ channels remain unclear. Some studies have reported that microRNAs (miRNAs) are involved in age-related cardiovascular diseases. Nevertheless, little is known about the roles of miRNAs in age-related SSS. This study investigated whether miR-1976 was involved in the regulation of SAN degeneration by targeting Ca(v)1.2 and Ca(v)1.3 Ca2+ channels. First, using microarray-based miRNA expression profiling and qRT-PCR, we confirmed that miR-1976 was upregulated in the plasma of patients with age-related SSS relative to healthy controls. By employing target gene prediction software, luciferase assay and western blotting, we further confirmed Ca(v)1.2 and Ca(v)1.3 as direct targets of miR-1976. Furthermore, miR-1976 levels in rabbit SAN tissues were negatively correlated with Ca(v)1.2 and Ca(v)1.3 expression and intrinsic heart rates but positively correlated with corrected sinus node recovery time (CSNRT). Additionally, miR-1976 transgenic mice displayed attenuated Ca(v)1.2 and Ca(v)1.3 protein expression, which led to sinus node dysfunction. These results suggest that miR-1976 plays an important role in the SAN aging process by targeting Ca(v)1.2 and Ca(v)1.3. Thus, miR-1976 could have great potential as a non-invasive diagnostic tool and therapeutic target for SSS. These findings may reveal important insights into the pathogenesis of SSS.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13015
专题	科研部门_发育的印迹调控与进化学（焦保卫）
推荐引用方式 GB/T 7714	Zhang, J,Wei, FY,Ding, LQ,et al. MicroRNA-1976 regulates degeneration of the sinoatrial node by targeting Ca(v)1.2 and Ca(v)1.3 ion channels[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2019,134:74-85.
APA	Zhang, J.,Wei, FY.,Ding, LQ.,Wang, LL.,Zhang, X.,...&Fan, J.(2019).MicroRNA-1976 regulates degeneration of the sinoatrial node by targeting Ca(v)1.2 and Ca(v)1.3 ion channels.JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,134,74-85.
MLA	Zhang, J,et al."MicroRNA-1976 regulates degeneration of the sinoatrial node by targeting Ca(v)1.2 and Ca(v)1.3 ion channels".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 134(2019):74-85.

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