RP11-789C1.1 inhibits gastric cancer cell proliferation and accelerates apoptosis via the ATR/CHK1 signaling pathway

Abstract

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 ataxia-telangiectasia 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.