Experimental Validation and Multi-omics Analysis Identified ARPC1A as a Novel Oncogene and Potential Therapeutic Target in Glioblastoma.

ABSTRACT

Actin-related protein 2/3 complex subunit 1A (ARPC1A) is implicated in several cancers due to its critical role in regulating actin polymerization. However, the exact mechanism of ARPC1A in cancer remains unclear. This study aims to investigate the biological role of ARPC1A in various cancers and the regulatory role of ARPC1A in glioblastoma multiforme (GBM). We analyzed the expression differences, prognostic value, mutations, immune infiltration, immune microenvironment, and single-cell level correlations of ARPC1A in various cancers. Furthermore, we employed gene set enrichment analysis (GSEA) and functional experiments to elucidate the regulatory mechanisms of ARPC1A on GBM. Importantly, we assessed the role of ARPC1A in temozolomide (TMZ) resistance of GBM. ARPC1A expression was up-regulated in most cancer tissues and was associated with poorer prognosis. Genomic mutation analysis revealed that the predominant type of ARPC1A mutation in tumors was amplification. ARPC1A expression was negatively correlated with B-cell and immune scores in most tumors. Both GSEA and single-cell sequencing have revealed that ARPC1A promotes tumor proliferation and epithelial-mesenchymal transition. In vitro experiments confirmed that ARPC1A knockdown inhibited the proliferation and metastatic ability of GBM cells. Notably, silencing ARPC1A reduced TMZ resistance in GBM cells. This study highlights the prognostic value of ARPC1A in various tumors and its potential for application in immunotherapy. Meanwhile, the modulation of GBM malignant behavior and TMZ resistance by ARPC1A provides a new approach for personalized and precise treatment of GBM.