ING5-mediated regulation of lung cancer progression via the OIP5-AS1/miR-381-3p/SEC24A axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths globally. It poses a significant threat to human health with high incidence and mortality rates. Current treatments like surgery, chemotherapy, and radiation have limited efficacy and often encounter drug resistance, highlighting the need for new therapeutic targets and strategies. The aim of this study was to assess how ING5 regulates lncOIP5-AS1, miR-381-3p, and SEC24A, and exerts its tumor-suppressive effects. METHODS: We developed NSCLC cell lines that overexpressed ING5 and transfected them with a miR-381-3p inhibitor and short hairpin RNA (shRNA) targeting long non-coding RNA (lncRNA) OIP5-AS1. The impact of lncRNA OIP5-AS1 on NSCLC cell proliferation, tumorigenesis, and migration was assessed using quantitative real-time polymerase chain reaction (qPCR), Western blot, cell cloning, Cell Counting Kit-8 (CCK-8) test, transwell invasion and migration assay, and subcutaneous tumorigenesis assay in nude mice. Bioinformatics methods were employed to predict the target genes of miR-381-3p, and the interaction with SEC24A was confirmed by a dual luciferase reporter gene test. RESULTS: The overexpression of ING5 markedly suppressed the proliferation, migration, and invasion of NSCLC. The inhibitory effect was counteracted by the overexpression of OIP5-AS1. miR-381-3p was markedly increased in cells overexpressing ING5 and interacted with the 3'UTR of SEC24A, suppressing its expression. SEC24A exhibited elevated expression in NSCLC and correlated with unfavorable prognosis. Animal studies demonstrated that the silencing of OIP5-AS1 suppressed tumor proliferation. CONCLUSIONS: Our cell-based and subcutaneous xenograft experiments suggest that ING5-mediated down-regulation of OIP5-AS1 may release miR-381-3p and consequently reduce SEC24A expression. However, this axis has not yet been validated in clinical specimens, and studies addressing metastasis or long-term toxicity are still needed.