Dysregulated Key Long Non-Coding Rnas Tp53tg1, Rfpl1s, Dleu1, and Hcg4 Associated With Epithelial-Mesenchymal Transition (Emt) in Castration-Resistant Prostate Cancer Publisher



Mehrabi T¹ ; Heidarzadehpilehrood R² ; Mobasheri M³ ; Sobati T³ ; Heshmati M¹ ; Pirhoushiaran M⁴
Source: Advances in Cancer Biology - Metastasis Published:2025

Abstract

Background: Castration-resistant prostate cancer (CRPC) is the severe and metastatic form of prostate cancer and demands effective, reliable diagnostic and therapeutic approaches. It has been shown that long non-coding RNAs (lncRNAs) dysregulations promote metastasis in tumors. The current research aim is to identify dysregulated lncRNAs in metastatic CRPC. Materials and methods: R programs along with multiple packages were applied to identify novel lncRNAs dysregulated in CRPC. Raw data of clinical samples were obtained from NCBI-GSE74685, which consisted of metastatic and non-metastatic CRPC samples, and was analyzed through a limma package of R with defined cutoff criteria as adjusted P-value < 0.05 and |Fold Change = FC| ≥ ±1. To further understand lncRNA co-expression gene modules, WGCNA analysis, hub-gene identification, and pathway enrichment were performed. Results: Four dysregulated lncRNAs were identified with more than a two-fold change in expression levels, including TP53TG1, RFPL1S, DLEU1, and HCG4. WGCNA analysis results in royal blue, salmon, light cyan, and blue co-expression modules with dysregulated lncRNAs. According to a pathway enrichment study, these co-expressed modules showed enrichment in highly relevant pathways to the CRPC metastatic process, including mesenchymal-to-epithelial transition, purine metabolism, C-MYB transcription factor network, and immune system. In addition, SOD2, PRKCA, IL6, and ITGAM were identified as hub genes. Conclusion: The current study suggests dysregulation of TP53TG1, RFPL1S, DLEU1, and HCG4 lncRNAs and corresponding hub genes may promote CRPC metastasis through the EMT pathways. © 2025 The Authors