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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
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Authors Affiliations
  1. 1. Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  2. 2. Department of Obstetrics & Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM, Serdang, Selangor, 43400, Malaysia
  3. 3. Department of Biotechnology, Tehran Islamic Azad University of Medical Sciences, Tehran, Iran
  4. 4. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

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
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