〔Abstract〕 Objective To investigate the expression of LncRNA PXN-AS1(abbreviated as PXN-AS1) in gastric cancer tissues and its impact on the proliferation, apoptosis, and invasion of gastric cancer cells, and to explore its potential regulatory mechanisms. Methods Gastric cancer tissues and adjacent tissues from 43 patients with gastric cancer were collected. The expression levels of PXN-AS1 and miR-125a-5p in gastric cancer tissues were detected using qRT-PCR, and the relationship between the expression level of PXN-AS1 and the clinical pathological parameters of patients with gastric cancer was analyzed. Pearson correlation analysis was conducted to evaluate the correlation between PXN-AS1 and miR-125a-5p in gastric cancer tissues. PXN-AS1 siRNA plasmid(si-PXN-AS1) and negative control plasmid(si-NC), as well as miR-125a-5p inhibitor(inhibitor) and negative control miRNA inhibitor(inhibitor NC), were transfected alone or in combination into HGC-27 cells. The cells were divided into si-NC group, si-PXN-AS1 group, si-PXN-AS1+inhibitor NC group, si-PXN-AS1+inhibitor group, and a blank control group was also established. qRT-PCR was utilized to assess the expression levels of PXN-AS1 and miR-125a-5p in each cell group. CCK-8 assay was employed to evaluate the proliferation levels of cells in each group. EdU experiment was conducted to assess the proliferation status of cells in each group. Transwell assay was performed to examine the migration and invasion capabilities of cells in each group; flow cytometry was employed to measure the apoptosis levels of cells in each group; the dual-luciferase reporter gene system was used to validate the sponge absorption of PXN-AS1 on miR-125a-5p and regulate its expression levels. Bioinformatics analysis was employed to screen downstream target genes of miR-125a-5p and perform GO and KEGG enrichment analysis. Results Compared with adjacent cancerous tissues, the expression level of the PXN-AS1 in gastric cancer tissues significantly increased, while the expression level of miR-125a-5p markedly decreased(bothP<0.05). PXN-AS1 and miR-125a-5p exhibited a negative correlation(r=-0.452,P=0.002). Furthermore, gastric cancer patients with high expression of PXN-AS1 exhibited the proportions of lymph node metastasis positivity and low differentiation were significantly higher(allP<0.05). Compared to the blank group and si-NC group, the si-PXN-AS1 group of HGC-27 cells showed significantly reduced levels of PXN-AS1 expression, cell proliferation capacity, and the number of cell migration and invasion(allP<0.05), while the level of cell apoptosis significantly increased(P<0.05). The dual-luciferase reporter system results demonstrated specific adsorption of miR-125a-5p by PXN-AS1 in HGC-27 cells. Knockdown of miR-125a-5p could reverse the effect of PXN-AS1 silencing on the inhibition of proliferation, migration and invasion of gastric cancer cells, and promote apoptosis. The bioinformatics analysis results indicated that the downstream target genes of miR-125a-5p were involved in various biological processes, including DNA damage, T cell apoptosis and differentiation, RNA metabolism synthesis processes, and signal transduction. Additionally, miR-125a-5p was implicated in signaling pathways such as the HIF-1 pathway, JAK-STAT pathway, and cell apoptosis signaling pathway. Conclusion PXN-AS1 is upregulated in gastric cancer. Moreover, acting as a competitive sponge for miR-125a-5p, PXN-AS1 promotes the proliferation, migration, and invasion abilities of gastric cancer cells HGC-27 while inhibiting apoptosis.