Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma.
Xue-Liang FangQing-Jie LiJia-Yi LinCheng-Long HuangSheng-Yan HuangXi-Rong TanShi-Wei HeXun-Hua ZhuJun-Yan LiSha GongHan QiaoYing-Qin LiNa LiuJun MaYin ZhaoLing-Long TangPublished in: Cell death & disease (2024)
Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients' survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.
Keyphrases
- cell proliferation
- transcription factor
- genome wide
- rna seq
- end stage renal disease
- gene expression
- single cell
- cell death
- locally advanced
- mass spectrometry
- newly diagnosed
- ejection fraction
- chronic kidney disease
- genome wide identification
- prognostic factors
- squamous cell carcinoma
- high throughput
- cell cycle arrest
- poor prognosis
- stem cells
- peritoneal dialysis
- rectal cancer
- big data
- circulating tumor cells
- high resolution
- smoking cessation
- pi k akt
- small molecule
- free survival
- dna binding
- risk assessment
- liquid chromatography
- data analysis
- artificial intelligence
- capillary electrophoresis