Unknown

Dataset Information

0

Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity.


ABSTRACT: The development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5-fluorouracil (5-FU) treatment in renal mesangial cells and kidney tissue, which was associated with decreased baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression and increased apoptotic rate. Enforced miR-181a expression enhanced 5-FU-induced p53-dependent mitochondrial apoptosis, including declined Bcl-2/Bax ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase-9 and caspase-3 activation. However, inhibition of miR-181a was associated with reduced p53-mediated mitochondrial apoptosis induced by 5-FU. Moreover, miR-181a increased BIRC6 downstream gene p53 protein expression and transcriptional activity by reducing ubiquitin-mediated protein degradation. We found that miR-181a directly targeted 3'-UTR of BIRC6 mRNA and negatively regulated BIRC6 expression. In vivo study, knockdown of miR-181a with adeno-associated virus harboring miR-181a-tough decoy attenuated 5-FU-induced renal cell apoptosis, inflammation and kidney injury. In conclusion, these results demonstrate that miR-181a increases p53 protein expression and transcriptional activity by targeting BIRC6 and promotes 5-FU-induced apoptosis in mesangial cells. Inhibition of miR-181a ameliorates 5-FU-induced nephrotoxicity, suggesting that miR-181a may be a novel therapeutic target for nephrotoxicity treatment during chemotherapy.

SUBMITTER: Liu XY 

PROVIDER: S-EPMC5966400 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

altmetric image

Publications

Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity.

Liu Xiao-Yun XY   Zhang Fei-Ran FR   Shang Jin-Yan JY   Liu Ying-Ying YY   Lv Xiao-Fei XF   Yuan Jia-Ni JN   Zhang Ting-Ting TT   Li Kai K   Lin Xiao-Chun XC   Liu Xiu X   Lei Qingqing Q   Fu Xiao-Dong XD   Zhou Jia-Guo JG   Liang Si-Jia SJ  

Cell death & disease 20180523 6


The development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5-fluorouracil (5-FU) treatment in renal mesangial cells and kidney tissue, which was associated with decreased baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression and incr  ...[more]

Similar Datasets

| S-EPMC4222721 | biostudies-literature
| S-EPMC7533499 | biostudies-literature
| S-EPMC7101871 | biostudies-literature
| S-EPMC7059292 | biostudies-literature
| S-EPMC6804466 | biostudies-literature
| S-EPMC5825286 | biostudies-literature
| S-EPMC7098399 | biostudies-literature
| S-EPMC6514581 | biostudies-literature
| S-EPMC4818264 | biostudies-literature
| S-EPMC3307705 | biostudies-literature