Objective: The long non-coding RNA DDX11 antisense RNA 1 (DDX11-AS1) was found to be highly expressed in gastric cancer (GC). This study was to explore the role and molecular mechanism in oxaliplatin (OXA) resistance.
Patients and methods: The levels of DDX11-AS1, microRNA-326 (miR-326) and insulin receptor substrate 1 (IRS1) were measured by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell proliferation, migration, invasion and apoptosis were examined by methylthiazolyldiphenyl-tetrazolium bromide (MTT), transwell and flow cytometry assays, respectively. Levels of all protein were detected using Western blot. The correlation between miR-326 and DDX11-AS1/IRS1 was confirmed by Dual-Luciferase reporter and RNA immunoprecipitation (RIP) assays. The xenograft model was constructed to explore the effect of DDX11-AS1 in vivo.
Results: DDX11-AS1 was overexpressed in OXA-resistant GC tissues and cells, and DDX11-AS1 knockdown inhibited cell proliferation, migration, invasion and OXA resistance, and promoted apoptosis in OXA-resistant GC cells. Mechanically, DDX11-AS1 directly targeted miR-326 and miR-326 could bind to IRS1 in OXA-resistant GC cells. Functionally, silencing DDX11-AS1 repressed the progression and OXA resistance in OXA-resistant GC cells by down-modulating IRS1 expression via sponging miR-326 in vitro and in vivo.
Conclusions: DDX11-AS1 accelerated the progression and OXA chemoresistance of GC cells in vitro and in vivo by sponging miR-326, thus increasing the expression of IRS1, suggesting DDX11-AS1 might be a promising prognostic biomarker and therapeutic target in GC.