Cholangiocarcinoma (CCA) remains a highly aggressive malignancy characterized by poor prognosis and limited response to standard therapies, despite recent advances in drug discovery. This highlights the urgent need for novel and more effective treatment strategies. In the context of precision medicine and molecularly targeted therapies, understanding the genetic and epigenetic mechanisms underlying CCA development and progression is crucial. This study aims to explore the role of Protein Arginine Methyltransferase 5 (PRMT5) in cholangiocarcinoma, focusing on its functional implications, molecular interactions, and potential as a therapeutic target. Experimental in vitro models were established to evaluate the effects of PRMT5 inhibition on CCA cell proliferation and viability using specific PRMT5 inhibitors. Given that PRMT5 forms a hetero-octameric complex with Methylosome Protein 50 (MEP50), the study also investigated MEP50 expression and its functional relationship with PRMT5. Preliminary evidence suggests that both PRMT5 and MEP50 are overexpressed in cholangiocarcinoma and may play a crucial role in tumor growth and progression. These findings contribute to the understanding of PRMT5-mediated oncogenic mechanisms and support the potential of PRMT5 as a novel therapeutic target in CCA.

Identification of PRMT5 as a therapeutic target in cholangiocarcinoma

MARIANI, STEFANO
2026

Abstract

Cholangiocarcinoma (CCA) remains a highly aggressive malignancy characterized by poor prognosis and limited response to standard therapies, despite recent advances in drug discovery. This highlights the urgent need for novel and more effective treatment strategies. In the context of precision medicine and molecularly targeted therapies, understanding the genetic and epigenetic mechanisms underlying CCA development and progression is crucial. This study aims to explore the role of Protein Arginine Methyltransferase 5 (PRMT5) in cholangiocarcinoma, focusing on its functional implications, molecular interactions, and potential as a therapeutic target. Experimental in vitro models were established to evaluate the effects of PRMT5 inhibition on CCA cell proliferation and viability using specific PRMT5 inhibitors. Given that PRMT5 forms a hetero-octameric complex with Methylosome Protein 50 (MEP50), the study also investigated MEP50 expression and its functional relationship with PRMT5. Preliminary evidence suggests that both PRMT5 and MEP50 are overexpressed in cholangiocarcinoma and may play a crucial role in tumor growth and progression. These findings contribute to the understanding of PRMT5-mediated oncogenic mechanisms and support the potential of PRMT5 as a novel therapeutic target in CCA.
26-feb-2026
Inglese
PUZZONI, MARCO
SCARTOZZI, MARIO
Università degli Studi di Cagliari
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/362983
Il codice NBN di questa tesi è URN:NBN:IT:UNICA-362983