FOXG1 Enhances Paclitaxel Resistance in Prostate Cancer via NANOG-Mediated Cellular Stemness

BackgroundPaclitaxel (PTX) is an effective chemotherapeutic agent for prostate cancer (PCa), yet resistance emerges with disease progression. Cancer-cell stemness is intimately linked to PTX resistance. This work clarifies whether FOXG1 modulates PTX resistance in PCa via cellular stemness.MethodsTCGA database was interrogated for FOXG1 expression in PCa. PTX-resistant PCa cell lines were generated by stepwise escalation of PTX concentration. qRT-PCR quantified FOXG1 and NANOG levels in PCa cells. CCK-8, sphere-formation assay, and flow cytometry evaluated cell viability, stemness, and apoptosis, respectively. Western blot assessed apoptosis-related proteins. JASPAR predicted FOXG1 binding sites within NANOG. Dual-luciferase reporter and ChIP verified FOXG1-NANOG interaction.ResultsBioinformatic analysis revealed elevated FOXG1 expression in PCa tissues. FOXG1 levels were likewise increased in PCa cells. A PTX-resistant PC-3 sub-line (PC-3-R) was established. FOXG1 silencing suppressed stemness and viability of PC-3-R cells under PTX exposure while promoting apoptosis. FOXG1 was identified as an upstream regulator of NANOG. NANOG overexpression reversed the effects conferred by FOXG1 silencing on PC-3-R cells.ConclusionFOXG1 fosters NANOG-mediated cellular stemness to potentiate PTX resistance in PCa.