Background and Objectives: Actin-related protein 2/3 complex subunit 1B (ARPC1B) is an essential subunit of the actin-related protein 2/3 (Arp2/3) complex. While there have been numerous research reports on Arp2/3 in relation to tumors, there needs to be more research on ARPC1B and its role in tumors, particularly at the pan-cancer level. Methods: Utilizing data from the cancer genome atlas (TCGA) and genotype-tissue expression (GTEx) databases, we analyzed ARPC1B expression differences in normal, tumor, and adjacent tissues, investigating its correlation with prognosis and clinical stages in various cancers. We conducted gene enrichment analysis and explored ARPC1B’s connection to the tumor immune microenvironment and its impact on anti-tumor drug resistance. In addition, in vivo and in vitro experiments have also been carried out to find the mechanism of ARPC1B on ovarian cancer (OV) proliferation and invasion. Results: ARPC1B was highly expressed in 33 tumor types, suggesting its role as a tumor-promoting factor. Its expression correlated with poor prognosis and served as a clinical staging marker in over 10 tumor types. ARPC1B is implicated in various biological processes and signaling pathways, uniquely associated with tumor immunity, indicating immunosuppressive conditions in high-expression cases. High ARPC1B expression was linked to resistance to six anti-tumor drugs. Further experiments showed that ARPC1B can affect the proliferation, apoptosis, migration, and invasion of OV cells through the AKT/PI3K/mTOR pathway. Conclusion: ARPC1B is a biomarker for immune suppression, prognosis, clinical staging, and drug resistance, providing new insights for cancer therapeutics.

Ovarian cancer represents one of the most prevalent gynecological malignancies with a poor prognosis. Targeting glycolytic pathways has emerged as a novel cancer therapeutic strategy. N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification plays a regulatory role in cancer glycolysis. Phosphoglycerate mutase 1 (PGAM1) functions as a critical glycolytic enzyme and potential therapeutic target in oncology. This study investigated the functional role and underlying mechanisms of NAT10 in ovarian cancer progression. Cellular glycolysis was assessed through glucose uptake measurements, lactate production quantification, and extracellular acidification rate analysis. Cell stemness characteristics were evaluated using sphere formation assays and western blot analysis. Molecular mechanisms were explored via quantitative real-time PCR, RNA immunoprecipitation (RIP), ac4C-specific RIP, dot blot analysis, and dual-luciferase reporter assays. Elevated NAT10 expression and ac4C modification levels were observed in ovarian cancer cells. NAT10 silencing significantly inhibited both cell stemness properties and glycolytic activity. Mechanistically, NAT10 enhanced PGAM1 mRNA stability through ac4C modification. Re-expression of PGAM1 reversed the functional effects induced by NAT10 depletion in ovarian cancer cells. Furthermore, in vivo tumor growth experiments demonstrated that NAT10 promotes tumorigenesis. Our findings demonstrate that NAT10 facilitates ovarian cancer progression by mediating ac4C modification of PGAM1. This study identifies a novel and potentially effective therapeutic target for ovarian cancer treatment.