Akademik Veri Yönetim Sistemi
16TH NATIONAL AND 2ND INTERNATIONAL CONGRESS OF HISTOLOGY AND EMBRYOLOGY, Sakarya, Türkiye, 26 - 28 Eylül 2024, ss.49
Abstract
Introduction: Prostate cancer is the second most common cancer type among men worldwide.
Androgen receptor signaling plays a significant role in its progression. In advanced stages,
androgen deprivation therapy is administered as the standard treatment to reduce androgen
levels. However, the side effects and loss of efficacy associated with this therapy decrease
patients’ quality of life, highlighting the need for additional therapeutic strategies.
Hydroxychloroquine (HCQ), an inhibitor of autophagy—a cellular degradation mechanism
pivotal in carcinogenesis—has been shown to enhance chemotherapy response in prostate
cancer patients and increase cytotoxicity in combination therapies. On the other hand,
reticulon 4 (RTN4), well-characterized in the nervous system, has been suggested in recent
studies to be involved in cell cycle regulation, viability, and immunomodulation in cancer,
although its cancer-related mechanisms remain largely unexplored.
Aim: This study aims to investigate the effect of HCQ on RTN4 mRNA expression in
androgen-dependent and -independent prostate cancer cells and to functionally annotate
potential HCQ-associated RTN4 protein interactors using in silico analysis.
Material-Method: The inhibition concentration (IC50) of HCQ, previously determined in our
study, were applied for 72 hours to androgen-dependent (LnCap) and androgen-independent
(PC3) prostate cancer cells at concentrations of 52 μM and 44.9 μM, respectively. After total
RNA isolation and subsequent cDNA synthesis, RTN4 expression levels were determined
using RT-PCR. Differences in expression between groups were analyzed using an unpaired ttest
with GraphPad Prism (v8.3.0). Finally, HCQ and RTN4 protein interaction networks were
constructed with data from the STITCH and STRING databases. Intersecting proteins within
these networks were identified through Cytoscape (v3.10.2), and functional annotation was
conducted using Enrichr.
Results: HCQ treatment increased RTN4 gene expression approximately 958-fold (p<0.0001)
in LnCap cells and 25-fold (p<0.05) in PC3 cells. KEGG annotation of HCQ-associated
RTN4 targets revealed significant involvement in cancer-related signaling pathways,
including those specific to prostate cancer (p<0.05). GO Biological Process analysis indicated
significant roles in apoptotic signaling regulation, cytokine response, and transmembrane
receptor signaling (p<0.05).
Conclusion: These findings indicate that RTN4 plays a significant role in prostate cancer,
especially in androgen-dependent cases, by affecting apoptosis, cytokine signaling, and
cancer-related pathways. HCQ may influence these processes by regulating RTN4 activity
beyond its effects on autophagy, suggesting its potential as a therapeutic agent for managing
prostate cancer. Future research should explore HCQ-associated RTN4 mechanisms to
enhance prostate cancer treatment strategies.