MicroRNA therapy confers anti-senescent effects on doxorubicin-related cardiotoxicity by intracellular and paracrine signaling.
MicroRNA therapy confers anti-senescent effects on doxorubicin-related cardiotoxicity by intracellular and paracrine signaling.
复制标题
DOI：
10.18632/aging.203743
复制
发表时间：
2021-12-05
期刊：
影响因子：
--
通讯作者：
Hou M
中科院分区：
文献类型：
--
作者：
Xia W;Chang B;Li L;Hu T;Ye J;Chen H;Li W;Zan T;Hou M
多柔比星（Dox）是一种重要的蒽环类抗生素，是一种有效的抗肿瘤药物，用于治疗实体瘤和恶性血液病。然而，其临床应用受到心脏毒性的阻碍。本研究旨在研究miR-199 a-3 p的心脏保护潜力。连续Dox治疗不仅显著诱导心肌细胞衰老，而且导致越来越多的衰老相关分泌表型（SASP）心肌细胞，经常导致心脏衰老。这项研究表明，当暴露于Dox时，心肌细胞中的miR-199 a-3 p下调。心脏特异性过表达miR-199 a-3 p促进细胞周期重新进入和细胞增殖，从而缓解心脏衰老。此外，miR-199 a-3 p的升高抑制了SASP的产生，从而阻碍了衰老的传播。在心肌细胞中，miR-199 a-3 p的调节改变了衰老相关蛋白GATA 4的水平。GATA 4的异位表达减弱了miR-199 a-3 p的抗衰老作用。总之，这些数据支持miR-199 a-3 p在Dox心脏毒性过程中的作用。miR-199 a-3 p的升高可能通过同时预防心脏衰老和减少衰老的扩散而在Dox心脏毒性治疗中提供双重治疗优势。
Doxorubicin (Dox), an important anthracycline, is a potent anticancer agent that is used for treating solid tumors and hematologic malignancies. However, its clinical use is hampered by cardiac cardiotoxicity. This study aimed to investigate the cardioprotective potential of miR-199a-3p. Continuous Dox treatment not only markedly induced cardiomyocyte senescence but also resulted in a growing number of senescence-associated secretory phenotype (SASP) cardiomyocytes, frequently leading to heart senescence. This study showed that miR-199a-3p was downregulated in cardiomyocytes when exposed to Dox. The cardiac-specific overexpression of miR-199a-3p promoted cell cycle re-entry and cell proliferation, resulting in relief from cardiac senescence. Also, the elevation of miR-199a-3p inhibited the generation of SASP, thus, hampering the spread of senescence. In cardiomyocytes, the modulation of miR-199a-3p changed the levels of senescence-related protein GATA4. The ectopic expression of GATA4 blunted the anti-senescence effect of miR-199a-3p. Together, the data supported a role for miR-199a-3p during Dox cardiotoxicity. The elevation of miR-199a-3p might provide a dual therapeutic advantage in Dox cardiotoxicity therapy by simultaneously preventing cardiac senescence and reducing the spread of senescence.
登录
查看更多内容
microRNA-199a-3p 通过靶向 PDCD4 抑制肝细胞凋亡和肝癌发生。
影响因子：
6.2
作者：
Li Z;Zhou Y;Zhang L;Jia K;Wang S;Wang M;Li N;Yu Y;Cao X;Hou J
通讯作者：
Hou J
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
64.8
作者：
Eulalio, Ana;Mano, Miguel;Giacca, Mauro
通讯作者：
Giacca, Mauro
影响因子：
37.8
作者：
Cardinale, Daniela;Colombo, Alessandro;Cipolla, Carlo M.
通讯作者：
Cipolla, Carlo M.
影响因子：
14
作者：
An, Minae;Kwon, Kihwan;Kim, Minsuk
通讯作者：
Kim, Minsuk