Integrative Multi-Omics Analysis Identifies NUP205 as a Candidate Prognostic Biomarker in Liver Hepatocellular Carcinoma

Patients with Liver Hepatocellular carcinoma (LIHC) have a poor prognosis due to late-stage diagnosis and the limited efficacy of drug treatments. Dysregulation of nuclear pore complex (NPC) components, particularly nucleoporins (NUPs), may play a role in tumor progression. However, the specific role of <i>NUP205</i> in LIHC has not been comprehensively investigated. We evaluated the expression, prognostic significance, epigenetic regulation, microRNA(miRNA) interactions, drug sensitivity, and biological functions of <i>NUP205</i> in LIHC. Comprehensive bioinformatics analyses were performed using publicly available databases and web-based analysis platforms, including The Cancer Genome Atlas (TCGA), UALCAN, and the Kaplan-Meier Plotter (KM Plotter), among others. <i>In vitro</i> validation was performed using small interfering RNA (siRNA)-mediated knockdown of <i>NUP205</i> in HepG2 cells, followed by quantitative reverse transcription PCR (RT-qPCR), apoptosis assay and wound-healing assay. <i>NUP205</i> expression was significantly elevated in patients with LIHC and was associated with advanced clinicopathological features and poor prognosis. Promoter hypomethylation and miRNAs were identified as regulatory mechanisms influencing <i>NUP205</i> expression. Increased <i>NUP205</i> levels were associated with resistance to multiple chemotherapeutic agents. <i>NUP205</i> knockdown significantly reduced messenger RNA (mRNA) expression in HepG2 and PLC/PRF/5 cells, and also reduced the expression of Transmembrane protein 209 (<i>TMEM209</i>) in HepG2 cells and improved sensitivity to doxorubicin. <i>NUP205</i> expression was consistently associated with adverse clinicopathological features, poor prognosis, and altered drug sensitivity in LIHC. Integrative analyses suggest that <i>NUP205</i> dysregulation may be linked to epigenetic and miRNA-associated regulatory mechanisms. These findings support <i>NUP205</i> as a candidate prognostic biomarker and a potential regulatory factor in LIHC, warranting further mechanistic and protein-level validation. Further research is necessary to fully elucidate its underlying mechanisms and potential clinical applications.