Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Cell death & disease - 15(2024), 2 vom: 06. Feb., Seite 112 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Fang, Xue-Liang [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 08.02.2024 Date Revised 12.02.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41419-024-06496-x |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368102254 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368102254 | ||
| 003 | DE-627 | ||
| 005 | 20240213232917.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240207s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41419-024-06496-x |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1291.xml |
| 035 | |a (DE-627)NLM368102254 | ||
| 035 | |a (NLM)38321024 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Fang, Xue-Liang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.02.2024 | ||
| 500 | |a Date Revised 12.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Docetaxel |2 NLM | |
| 650 | 7 | |a 15H5577CQD |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a Fluorouracil |2 NLM | |
| 650 | 7 | |a U3P01618RT |2 NLM | |
| 650 | 7 | |a Cisplatin |2 NLM | |
| 650 | 7 | |a Q20Q21Q62J |2 NLM | |
| 650 | 7 | |a USP10 protein, human |2 NLM | |
| 650 | 7 | |a Ubiquitin Thiolesterase |2 NLM | |
| 650 | 7 | |a EC 3.4.19.12 |2 NLM | |
| 650 | 7 | |a ATMIN protein, human |2 NLM | |
| 700 | 1 | |a Li, Qing-Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Jia-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Cheng-Long |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Sheng-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Xi-Rong |e verfasserin |4 aut | |
| 700 | 1 | |a He, Shi-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xun-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jun-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Sha |e verfasserin |4 aut | |
| 700 | 1 | |a Qiao, Han |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ying-Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Ling-Long |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell death & disease |d 2010 |g 15(2024), 2 vom: 06. Feb., Seite 112 |w (DE-627)NLM202030881 |x 2041-4889 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g number:2 |g day:06 |g month:02 |g pages:112 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41419-024-06496-x |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |e 2 |b 06 |c 02 |h 112 | ||