标题:lncRNA-XIST protects the hypoxia-induced cardiomyocyte injury through regulating the miR-125b-hexokianse 2 axis
作者:Fan, Ji-Lin; Zhu, Ting-Ting; Xue, Zhen-Yu; Ren, Wen-Qing; Guo, Jing-Qi; Zhao, Heng-Yi; Zhang, Shi-Liang
作者机构:[Fan, Ji-Lin; Xue, Zhen-Yu; Ren, Wen-Qing; Guo, Jing-Qi] Shandong Univ Tradit Chinese Med, Jinan 250355, Shandong, Peoples R China.; [Zhu, Ting-Ting 更多
通讯作者:Zhang, SL(zhangshiliangsd@126.com)
通讯作者地址:Zhang, SL (corresponding author), Shandong Univ Tradit Chinese Med, Dept Cardiol, Affiliated Hosp, 16369 Jingshi Rd, Jinan 250014, Shandong, Peoples R 更多
来源:IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
出版年:2020
卷:56
期:4
页码:349-357
DOI:10.1007/s11626-020-00459-0
关键词:Cardiomyocyte injury; Hypoxia; lncRNA-XIST; miRNA-125b; Glucose; metabolism
摘要:Ischemic injury in the heart is associated with low oxygen, leading to the damage of cardiomyocytes. The lncRNA-XIST is known to involve in post-ischemia myocardial remodeling. However, the roles and mechanism of XIST in the hypoxia-induced cardiomyocyte are still under investigation. Moreover, studies that elucidated the impaired glucose metabolism present new hallmark of ischemic cardiovascular injury. The objective of this study is to investigate the effects of lncRNA-XIST on cardiomyocyte injury under hypoxia. Here, we demonstrate that the XIST expressions of cardiomyocyte line, H9c2 were apparently suppressed by long-time hypoxia exposure under low glucose supply. On the contrary, miRNA-125b showed reverse expression pattern to XIST. We identified that XIST functioned as a ceRNA of miR-125b to downregulate its expression in both cell line and rat primary cardiomyocyte. Under low glucose supply, H9c2 cells exhibited increased susceptibility to hypoxia. We observed overexpression of XIST significantly elevated glycose metabolism rate under hypoxia, but overexpression of miR-125b inhibited glycose metabolism rate of cardiomyocyte under hypoxia. The glycolysis enzyme, hexokinase 2 (HK2) was validated as a direct target of miR-125b, which binds to the 3 '-UTR region of HK2 mRNA in cardiomyocytes. Moreover, inhibition of miR-125b significantly protected the hypoxia-induced cardiomyocyte injury through restoration of glucose metabolism. Finally, we demonstrated that transfection of miR-125b in lncRNA-XIST overexpressed H9c2 cells effectively abolished the XIST-activated glucose metabolism and cardiomyocyte protection under hypoxia. The present study illustrates roles of the XIST-miR-125b-HK2 axis in the hypoxia-induced cardiomyocyte injury and proposes that maintaining glucose metabolism might be an effective approach for protection of cardiomyocyte injury.
收录类别:SCOPUS;SCIE
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084733363&doi=10.1007%2fs11626-020-00459-0&partnerID=40&md5=265dcbcb88b10f5d41166871454e56bf
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