LncRNA DYNLRB2-AS1 promotes gemcitabine resistance of nasopharyngeal carcinoma by inhibiting the ubiquitination degradation of DHX9 protein.
Drug Resist Updat
; 76: 101111, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38908233
ABSTRACT
Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15â¯% of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated lncRNAs, of which, DYNLRB2-AS1 was one of the most upregulated lncRNAs in GEM-resistance NPC cell lines. DYNLRB2-AS1 was shown to function as contain an oncogenic lncRNA that promoted NPC GEM resistance, cell proliferation, but inhibited cell apoptosis. Mechanistically, DYNLRB2-AS1 could directly bind to the DHX9 protein and prevent its interaction with the E3 ubiquitin ligase PRPF19, and thus blocking PRPF19-mediated DHX9 degradation, which ultimately facilitated the repair of DNA damage in the presence of GEM. Clinically, higher DYNLRB2-AS1 expression indicated an unfavourable overall survival of NPC patients who received induction chemotherapy. Overall, this study identified the oncogenic lncRNA DYNLRB2-AS1 as an independent prognostic biomarker for patients with locally advanced NPC and as a potential therapeutic target for overcoming GEM chemoresistance in NPC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nasopharyngeal Neoplasms
/
Deoxycytidine
/
DEAD-box RNA Helicases
/
RNA, Long Noncoding
/
Nasopharyngeal Carcinoma
/
Gemcitabine
Limits:
Animals
/
Humans
Language:
En
Journal:
Drug Resist Updat
Journal subject:
ANTINEOPLASICOS
Year:
2024
Type:
Article