HOXA10-AS Enhances Gastric Cancer Cell Proliferation, Migration, and Invasion via the p38 MAPK/STAT3 Signaling Pathway

Gastric Cancer (GC) represents a major global health concern, with over 1 million new cases diagnosed annually worldwide. Emerging studies have highlighted the significant correlation between long noncoding RNAs (lncRNAs) and the progression of GC. The objective of the current study is to investigate the roles and mechanism of lncRNA homeobox A10 antisense RNA (HOXA10-AS) in modulating malignant properties of GC cells. RT-qPCR was employed to detect HOXA10-AS expression in GC cells or human normal gastric epithelium cells. The cellular localization of HOXA10-AS and mRNA HOXA10 were detected using RNA fractionation assays. Colony forming assays and Transwell assays were performed to assess the proliferative, invasive, and migratory capabilities of GC cells. Western blot analysis was used to determine protein levels of epithelial mesenchymal transition (EMT) markers in GC cells. RNA immunoprecipitation, RNA pulldown assays and luciferase assays were conducted to explore gene interaction. As shown by experimental results, HOXA10-AS showed high expression in GC cells. The silencing of HOXA10-AS led to weakened proliferative, invasive, and migratory abilities of GC cells, as well as inhibition of the EMT process. Moreover, HOXA10-AS positively regulated HOXA10 expression by interacting with miR-29a/b/c-3p. Additionally, overexpression of HOXA10 counteracted the repressive impacts on malignant cellular process caused by the knockdown of HOXA10-AS. Furthermore, HOXA10-AS activated the p38 MAPK/STAT3 signaling pathway via upregulation of HOXA10. In conclusion, HOXA10-AS upregulates HOXA10 expression through interaction with miR-29a/b/c-3p. The resultant increase in HOXA10 expression activates the p38 MAPK/STAT3 signaling, thereby promoting GC cell growth, migration, invasion, and EMT process.

HOXA10; HOXA10‐AS; STAT3; gastric cancer; p38 MAPK.