LncRNA XIST enhances gastric cancer cell function by regulating STAT3/PD-L1 axis as a competing endogenous RNA for miR-124.

OBJECTIVE

To investigate the role and underlying mechanisms of the long non-coding RNA (lncRNA) X inactive-specific transcript (XIST) in gastric cancer (GC).

METHODS

Real-time quantitative PCR (RT-qPCR), CCK-8, colony formation, flow cytometry, Transwell, and scratch assays were used to evaluate the biological effects of XIST and miR-124 in GC cells. Bioinformatics analysis and dual-luciferase reporter (DLR) assays identified interactions between XIST, miR-124, and STAT3. Western blotting and RT-qPCR assessed changes in downstream targets, while a xenograft tumor model evaluated the in vivo effects of XIST knockdown.

RESULTS

XIST was significantly upregulated, and miR-124 was downregulated in GC tissues and cell lines, with the strongest effects observed in MGC803 cells. Knockdown of XIST or overexpression of miR-124 suppressed GC cell proliferation, colony formation, migration, invasion, and promoted apoptosis, effects that were reversed by miR-124 inhibitors. Bioinformatics and DLR assays confirmed that XIST directly targeted miR-124 and regulated STAT3 expression. XIST knockdown increased miR-124 levels, reducing STAT3, PD-1, PD-L1, N-cadherin, and MMP9 expression, while elevating E-cadherin levels; these effects were reversed by miR-124 inhibitors. Additionally, sh-STAT3 mitigated the pro-tumorigenic effects of pcDNA-XIST, confirming the regulatory relationship. In vivo, XIST knockdown suppressed tumor growth by increasing miR-124 expression.

CONCLUSION

XIST promotes STAT3 expression by competitively binding to miR-124, thereby promoting GC progression. Targeting the XIST/miR-124/STAT3 axis may represent a potential therapeutic strategy for GC.