RP11-789C1.1 inhibits gastric cancer cell proliferation and accelerates apoptosis via the ATR/CHK1 signaling pathway
10.1097/CM9.0000000000002869
- VernacularTitle:RP11-789C1.1 inhibits gastric cancer cell proliferation and accelerates apoptosis via the ATR/CHK1 signaling pathway
- Author:
Wenwei LIU
1
;
Wei FENG
;
Yongxin ZHANG
;
Tianxiang LEI
;
Xiaofeng WANG
;
Tang QIAO
;
Zehong CHEN
;
Wu SONG
Author Information
1. Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518000, China
- Keywords:
Long non-coding RNA;
RP11-789C1.1;
Stomach neoplasms;
ATR;
CHK1;
Oxaliplatin
- From:
Chinese Medical Journal
2024;137(15):1835-1843
- CountryChina
- Language:Chinese
-
Abstract:
Background::Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods::We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results::Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity.Conclusion::In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.
