| RRC ID |
86829
|
| Author |
Ma Z, Xu Z, Xu J, Chen C, Niu W, Wang Y, Qian Y, Zhang X, Yang M, Stefan SM, Gan L, Wang S, Wang B.
|
| Title |
RNA-binding motif protein 15 promotes gastric cancer growth and drug resistance via USP10-mediated deubiquitination and stabilization of nuclear NRF2.
|
| Journal |
Drug Resist Updat
|
| Abstract |
Gastric cancer (GC) continues to pose a major global health burden for which chemotherapy remains a first-line treatment. However, the efficacy of chemotherapy is often compromised by the development of chemoresistance, the underlying mechanisms of which remain elusive. Here, by profiling nascent RNA-binding proteins (nRBPs) and chromatin-binding proteins (chrBPs) in GC organoids, we identified RNA-binding motif protein 15 (RBM15) as a chromatin-associated nRBP (chr-nRBP) that is upregulated in GC cells and promotes tumour growth and chemoresistance. Mechanistically, RBM15 contains a microtubule-associated protein 1 A/1B-light chain 3 (LC3)-interacting region (LIR) motif, which is directed to the lysosome through autophagy, and impaired nucleophagy leads to its accumulation in tumours. Accumulated RBM15 recruits ubiquitin-specific peptidase 10 (USP10) to the nucleus, where it deubiquitinates and stabilizes nuclear factor erythroid 2-related factor 2 (NRF2), thereby decreasing its proteasome-mediated degradation. This RBM15-USP10-NRF2 axis drives resistance to cisplatin and 5-fluorouracil (5-FU) both in vitro and in vivo. Disruption of this pathway sensitizes GC cells to chemotherapy and suppresses tumour growth. Collectively, our findings suggest that RBM15 is both a predictive biomarker and a therapeutic target for overcoming chemotherapy resistance in GC cells.
|
| Volume |
86
|
| Pages |
101376
|
| Published |
2026-2-10
|
| DOI |
10.1016/j.drup.2026.101376
|
| PII |
S1368-7646(26)00027-0
|
| PMID |
41702032
|
| Resource |
| Human and Animal Cells |
MKN45(RCB1001) |
