Abstract
<title>Abstract</title> <p>Glioma, a common and aggressive brain tumor, has a poor prognosis. Long noncoding RNAs (lncRNAs) are crucial in tumor development, though their roles are not fully understood. This study identified the lncRNA PAXIP1-AS2 using integrated analysis and cross-validation across multiple cohorts, assessing its expression and prognostic value through bioinformatics and public databases. Patients were divided into high and low expression groups for differential gene analysis, with functional enrichment via GO, KEGG, and GSEA. Results showed PAXIP1-AS2-related genes were involved in extracellular matrix (ECM) remodeling and cell adhesion. The qRT-PCR assay confirmed its high expression in glioma cell lines. A series of in vitro assays demonstrated that the downregulation of PAXIP1-AS2 expression significantly inhibits glioma cell proliferation, induces apoptosis, causes arrest in the G2/M phase, and reduces cell migration and invasion, thereby highlighting its critical role in tumor proliferation, apoptosis, cell cycle regulation, and invasiveness. Drug sensitivity analysis shows that gliomas with high PAXIP1-AS2 levels are more responsive to RTK/PI3K-mTOR inhibitors but resistant to histone acetylation-targeting drugs. Overall, PAXIP1-AS2 is vital for glioma progression, with high expression associated with malignancy and poor prognosis, making it a potential prognostic biomarker and therapeutic target.</p>