SPINT1-AS1 promotes oxidative damage and apoptosis of gastric cancer cells via the miR-656-3p/PLCXD3 axis.

[BACKGROUND AND OBJECTIVES] In the study of gastric cancer (GC), long non-coding RNAs (lncRNAs) have been identified and their functions have been partly characterized; however, the specific function of SPINT1 antisense RNA 1 (SPINT1-AS1) in GC remains unclear. This study aimed to investigate the role of SPINT1-AS1 in GC cells and elucidate its downstream molecular mechanisms.

[METHODS] SPINT1-AS1, microRNA-656-3p (miR-656-3p), and phospholipase C, X domain containing 3 (PLCXD3) levels were modulated in GC cells through transfection experiments. Quantitative reverse transcription polymerase chain reaction and Western blot analyses were performed to assess SPINT1-AS1, miR-656-3p, and PLCXD3 levels. The proliferative capacity, apoptosis, invasion, migration, and oxidative stress levels of GC cells were evaluated using 5-ethynyl-2'-deoxyuridine assay, colony formation assay, flow cytometry, Transwell assays, and commercial kits, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to assess the targeting relationships among SPINT1-AS1, miR-656-3p, and PLCXD3. The impact of SPINT1-AS1 on GC tumor growth was examined in xenograft tumor models.

[RESULTS] SPINT1-AS1 and PLCXD3 were found to be downregulated in GC, whereas miR-656-3p was upregulated. SPINT1-AS1 elevation inhibited GC cell proliferation, invasion, migration, and oxidative stress, and promoted apoptosis. SPINT1-AS1 knockdown had opposite effects. The pro-tumor effects induced by SPINT1-AS1 knockdown were reversed by concomitant knockdown of miR-656-3p. Similarly, the inhibitory effects of SPINT1-AS1 elevation on GC malignancy were abrogated by PLCXD3 knockdown. SPINT1-AS1 knockdown suppressed GC tumor growth in mice. SPINT1-AS1 competitively bound to miR-656-3p to mediate PLCXD3 expression.

[CONCLUSIONS] SPINT1-AS1 suppresses GC malignancy through the regulation of the miR-656-3p/PLCXD3 axis. These findings provide robust data supporting the biological functions of lncRNAs in GC and offer potential targets for therapeutic intervention.