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

## TL;DR

This study identifies NUP205 as a potential biomarker for liver cancer prognosis and drug resistance, based on multi-omics analysis and in vitro experiments.

## Contribution

The novel contribution is the comprehensive investigation of NUP205's role in liver hepatocellular carcinoma, including its epigenetic regulation and drug sensitivity associations.

## Key findings

- NUP205 expression is elevated in liver hepatocellular carcinoma and linked to poor prognosis and advanced clinicopathological features.
- Promoter hypomethylation and miRNA interactions regulate NUP205 expression in liver cancer.
- NUP205 knockdown reduces mRNA levels and increases sensitivity to doxorubicin in liver cancer cells.

## Abstract

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 NUP205 in LIHC has not been comprehensively investigated. We evaluated the expression, prognostic significance, epigenetic regulation, microRNA(miRNA) interactions, drug sensitivity, and biological functions of NUP205 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. In vitro validation was performed using small interfering RNA (siRNA)-mediated knockdown of NUP205 in HepG2 cells, followed by quantitative reverse transcription PCR (RT-qPCR), apoptosis assay and wound-healing assay. NUP205 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 NUP205 expression. Increased NUP205 levels were associated with resistance to multiple chemotherapeutic agents. NUP205 knockdown significantly reduced messenger RNA (mRNA) expression in HepG2 and PLC/PRF/5 cells, and also reduced the expression of Transmembrane protein 209 (TMEM209) in HepG2 cells and improved sensitivity to doxorubicin. NUP205 expression was consistently associated with adverse clinicopathological features, poor prognosis, and altered drug sensitivity in LIHC. Integrative analyses suggest that NUP205 dysregulation may be linked to epigenetic and miRNA-associated regulatory mechanisms. These findings support NUP205 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.