MiR-30c regulates cisplatin-induced apoptosis of renal tubular epithelial cells by targeting Bnip3L and Hspa5.
MiR-30c regulates cisplatin-induced apoptosis of renal tubular epithelial cells by targeting Bnip3L and Hspa5.
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DOI：
10.1038/cddis.2017.377
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发表时间：
2017-08-10
影响因子：
9
通讯作者：
Yang XS
中科院分区：
文献类型：
--
作者：
Du B;Dai XM;Li S;Qi GL;Cao GX;Zhong Y;Yin PD;Yang XS
顺铂作为一种常用的抗肿瘤药物，已广泛应用于临床肿瘤治疗。但顺铂的毒副作用，尤其是肾毒性，明显限制了顺铂的应用。因此，研究肾损伤的机制并探索相应的治疗方法势在必行。在这项研究中，我们显示了肾小管和上皮细胞死亡的表型，以及升高的切割半胱天冬酶3和TUNEL阳性细胞在大鼠腹腔注射顺铂。在HK-2和NRK-52 E细胞中也发现类似的顺铂诱导的细胞凋亡。在体内和体外顺铂诱导的细胞凋亡模型中，定量PCR数据显示miR-30 a-e表达水平降低，表明miR-30可能参与调控顺铂诱导的细胞凋亡。当发现顺铂诱导的细胞凋亡的作用与miR-30 c表达的改变密切相关时，这一点得到了进一步证实，miR-30 c表达的改变是通过在HK-2和NRK-52 E细胞中转染miR-30 c模拟物或miR-30 c抑制剂来操纵的。利用TargetScan和基因表达数据库（Gene Expression Omnibus）等生物信息学工具，预测Adrb 1、Bnip 3L、Hspa 5和MAP 3 K12为miR-30 c在顺铂诱导的细胞凋亡中的靶基因。随后，在HK-2细胞中操纵miR-30 c表达水平后，确定这些推定基因的表达后，确认Bnip 3L和Hspa 5是靶基因。综上所述，我们目前的实验表明miR-30 c确实参与了顺铂诱导的肾小管细胞凋亡的调控，这可能为减少顺铂诱导的肾毒性提供了一种新的策略。
As a common anticancer drug, cisplatin has been widely used for treating tumors in the clinic. However, its side effects, especially its nephrotoxicity, noticeably restrict the application of cisplatin. Therefore, it is imperative to investigate the mechanism of renal injury and explore the corresponding remedies. In this study, we showed the phenotypes of the renal tubules and epithelial cell death as well as elevated cleaved-caspase3- and TUNEL-positive cells in rats intraperitoneally injected with cisplatin. Similar cisplatin-induced cell apoptosis was found in HK-2 and NRK-52E cells exposed to cisplatin as well. In both models of cisplatin-induced apoptosis in vivo and in vitro, quantitative PCR data displayed reductions in miR-30a-e expression levels, indicating that miR-30 might be involved in regulating cisplatin-induced cell apoptosis. This was further confirmed when the effects of cisplatin-induced cell apoptosis were found to be closely correlated with alterations in miR-30c expression, which were manipulated by transfection of either the miR-30c mimic or miR-30c inhibitor in HK-2 and NRK-52E cells. Using bioinformatics tools, including TargetScan and a gene expression database (Gene Expression Omnibus), Adrb1, Bnip3L, Hspa5 and MAP3K12 were predicted to be putative target genes of miR-30c in cisplatin-induced apoptosis. Subsequently, Bnip3L and Hspa5 were confirmed to be the target genes after determining the expression of these putative genes following manipulation of miR-30c expression levels in HK-2 cells. Taken together, our current experiments reveal that miR-30c is certainly involved in regulating the renal tubular cell apoptosis induced by cisplatin, which might supply a new strategy to minimize cisplatin-induced nephrotoxicity.
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Micro-RNA-30a 通过靶向原代培养的皮质神经元和中风后小鼠大脑中的热休克蛋白 HSPA5 来调节缺血诱导的细胞死亡
影响因子：
4.2
作者：
Wang, Peng;Zhang, Nan;Li, Junfa
通讯作者：
Li, Junfa
影响因子：
5.7
作者：
Bhatt, Kirti;Zhou, Li;Dong, Zheng
通讯作者：
Dong, Zheng
影响因子：
48
作者：
Mullokandov, Gavriel;Baccarini, Alessia;Ruzo, Albert;Jayaprakash, Anitha D.;Tung, Navpreet;Israelow, Benjamin;Evans, Matthew J.;Sachidanandam, Ravi;Brown, Brian D.
通讯作者：
Brown, Brian D.
DOI：
10.1152/ajprenal.00486.2016
发表时间：
2017-04-01
影响因子：
4.2
作者：
Guo, Yan;Deng, Xu;Zhang, Aihua
通讯作者：
Zhang, Aihua
影响因子：
3
作者：
Gutierrez-Escolano, A.;Santacruz-Vazquez, E.;Gomez-Perez, F.
通讯作者：
Gomez-Perez, F.