LncRNA-H19 Drives Cardiomyocyte Senescence by Targeting miR-19a/socs1/p53 Axis.
LncRNA-H19 Drives Cardiomyocyte Senescence by Targeting miR-19a/socs1/p53 Axis.
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LncRNA-H19 通过靶向 miR-19a/socs1/p53 轴驱动心肌细胞衰老
DOI：
10.3389/fphar.2021.631835
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Zhuang Y;Li T;Xiao H;Wu J;Su S;Dong X;Hu X;Hua Q;Liu J;Shang W;Ju J;Sun F;Pan Z;Lu Y;Zhang M
目的：心肌细胞衰老与心脏生理功能的进行性下降和心血管事件的风险有关。lncRNA H19（H19）是一种已知的长链非编码RNA（longnoncodingRNA，lncRNA），参与心力衰竭、心肌缺血和纤维化等多种心血管疾病的病理生理过程。然而，H19在心肌细胞衰老中的作用仍有待进一步研究。方法：采用衰老相关β-半乳糖苷酶（SA-β-gal）染色法检测心肌细胞衰老。采用Western blot、qRT-PCR和荧光素酶报告基因分析等方法研究H19在心肌细胞衰老中的作用及其分子机制。结果：高糖诱导的衰老心肌细胞和衰老小鼠心脏中H19水平显著升高。H19的过表达增加了SA-β-gal阳性细胞的数量，以及衰老相关蛋白p53和p21的表达，而H19的敲低则产生相反的效果。从机制上讲，H19被证明是microRNA-19 a（miR-19 a）的竞争性内源RNA（ceRNA）：H19过表达下调miR-19 a水平，而H19敲低上调miR-19 a。SOSC 1在衰老心肌细胞和老年小鼠心脏中的表达显著增加。进一步的实验将SOCS 1鉴定为miR-19 a的下游靶标。H19通过靶向miR-19 a上调SOCS 1表达并激活p53/p21通路，从而促进心肌细胞衰老。结论：H19是心肌细胞中的促衰老lncRNA，作为ceRNA靶向miR-19 a/SOCS 1/p53/p21通路。本研究揭示了心肌细胞衰老调控的分子机制，为衰老相关心脏疾病的治疗提供了新的靶点。
Purpose: Cardiomyocyte senescence is associated with a progressive decline in cardiac physiological function and the risk of cardiovascular events. lncRNA H19 (H19), a well-known long noncoding RNA (lncRNA), is involved in the pathophysiological process of multiple cardiovascular disease such as heart failure, cardiac ischemia and fibrosis. However, the role of H19 in cardiomyocyte senescence remains to be further explored. Methods: Senescence-associated β-galactosidases (SA-β-gal) staining was used to detect cardiomyocyte senescence. Western blot, qRT-PCR and luciferase reporter assay were employed to evaluate the role of H19 in cardiomyocyte senescence and its underling molecular mechanism. Results: H19 level was significantly increased in high glucose-induced senescence cardiomyocytes and aged mouse hearts. Overexpression of H19 enhanced the number of SA-β-gal-positive cells, and the expression of senescence-related proteins p53 and p21, whereas H19 knockdown exerted the opposite effects. Mechanistically, H19 was demonstrated as a competing endogenous RNA (ceRNA) for microRNA-19a (miR-19a): H19 overexpression downregulated miR-19a level, while H19 knockdown upregulated miR-19a. The expression of SOSC1 was dramatically increased in senescence cardiomyocytes and aged mouse hearts. Further experiments identified SOCS1 as a downstream target of miR-19a. H19 upregulated SOCS1 expression and activated the p53/p21 pathway by targeting miR-19a, thus promoting the cardiomyocytes senescence. Conclusion: Our results show that H19 is a pro-senescence lncRNA in cardiomyocytes acting as a ceRNA to target the miR-19a/SOCS1/p53/p21 pathway. Our research reveals a molecular mechanism of cardiomyocyte senescence regulation and provides a novel target of the therapy for senescence-associated cardiac diseases.
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影响因子：
10.8
作者：
Hofmann P;Sommer J;Theodorou K;Kirchhof L;Fischer A;Li Y;Perisic L;Hedin U;Maegdefessel L;Dimmeler S;Boon RA
通讯作者：
Boon RA
高葡萄糖通过上调自噬来诱导骨髓来源的间充质干细胞衰老。
影响因子：
3.7
作者：
Chang TC;Hsu MF;Wu KK
通讯作者：
Wu KK
DOI：
10.1073/pnas.0806202105
发表时间：
2008-09-02
影响因子：
11.1
作者：
Pichiorri, Flavia;Suh, Sung-Suk;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
影响因子：
56.9
作者：
Azzalin, Claus M.;Reichenbach, Patrick;Lingner, Joachim
通讯作者：
Lingner, Joachim
lncRNA H19 通过抑制 miR-877-3p/Bcl-2 介导的线粒体凋亡减轻心肌 I/RI
影响因子：
8.8
作者：
Li, Xin;Luo, Shenjian;Lu, Yanjie
通讯作者：
Lu, Yanjie