NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE212122 Query DataSets for GSE212122
Status Public on Sep 20, 2023
Title RNA-seq analysis revealed that chloroquine(CQ) intervenes nephrotoxicity of nilotinib in an autophagy-independent manner
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Nilotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor for the first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia. However, its nephrotoxicity has become prominent with the increase of clinical use, which greatly limits its long-term application. So far, the mechanism of nilotinib’s nephrotoxicity is still unknown leading to a lack of clinical intervention strategies. Here, we found that nilotinib could promote intrinsic apoptosis of both vascular endothelial cells and renal tubular epithelial cells, which was mediated by the excessive ubiquitin-proteasome degradation of anti-apoptotic protein BCL-XL. Moreover, we confirmed that Chloroquine (CQ) could intervene nilotinib-induced apoptosis by reversing the decreased BCL-XL whose mechanism was not relied on autophagy inhibition. Furthermore, RNA-seq analysis was applied to identify the potential target of CQ and the result suggested that CQ could alleviate nilotinib-induced ANKRD1 reduction. Further, we found ANKRD1 abrogated cell apoptosis by preventing ubiquitination of BCL-XL and hence inhibiting BCL-XL degradation. In conclusion, our research reveals the molecular mechanism of nilotinib’s nephrotoxicity, wherein the excessive degradation of BCL-XL via ubiquitin-proteasome pathway promotes kidney cells apoptosis, and provides CQ analogs as the clinical intervention strategy of nilotinib’s nephrotoxicity whose pharmacological effect is dependent on ANKRD1 instead of autophagy inhibition.
 
Overall design Control Sample, Nilotinib-treated Sample, CQ-treated Sample, Nilotinib plus CQ-treated Sample
 
Contributor(s) Yan H, LUO P
Citation(s) 37452432
Submission date Aug 26, 2022
Last update date Sep 21, 2023
Contact name huang xiangliang
E-mail(s) huangxiangliang@zju.edu.cn
Phone 17794517278
Organization name zhejiang university
Street address hanzghou, China
City hangzhou
ZIP/Postal code 310012
Country China
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (4)
GSM6509741 Control
GSM6509742 Nilotinib
GSM6509743 CQ
Relations
BioProject PRJNA874052

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE212122_RAW.tar 5.3 Mb (http)(custom) TAR (of XLS)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap
External link. Please review our privacy policy.