Tumor-suppressive miR-299-3p inhibits gastric cancer cell invasion by targeting heparanase

Gastric cancer (GC) remains a leading cause of cancer-associated mortality globally. Emerging evidence suggests that microRNAs (miRs) function as oncogenes or tumor suppressors, contributing to various aspects of cancer progression, including invasion and metastasis. In the present study, the specific role of miR-299-3p in the invasion of GC cells was investigated. The expression level of miR-299-3p was measured using reverse transcription-quantitative PCR and in situ hybridization in human GC tissues. Effects of miR-299-3p on GC cell invasion were determined by Transwell assay. Bioinformatics and luciferase reporter assays were performed to identify and verify the downstream effectors of miR-299-3p. miR-299-3p expression analysis in clinical GC samples revealed a significant downregulation of miR-299-3p compared with non-tumor tissues. Inhibition of miR-299-3p promoted the invasive abilities of GC cells, whereas its overexpression significantly suppressed cell invasion. Bioinformatics and luciferase reporter assays identified heparanase (HPSE) as a direct target of miR-299-3p, the ectopic expression of which reversed the impairment in cell invasion induced by miR-299-3p upregulation. Furthermore, HPSE expression was negatively associated with miR-299-3p levels in human GC tissues. Overall, the present study indicated that miR-299-3p functions as a tumor suppressor by directly targeting HPSE, highlighting its potential as a target for the treatment of GC.