4.7 Review

Protein arginine N-methyltransferase 5 in colorectal carcinoma: Insights into mechanisms of pathogenesis and therapeutic strategies

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 145, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.112368

Keywords

PRMT5; Colorectal cancer; Epigenetics; Histone modification; Theranostics

Funding

  1. Al-Jalila Foundation, Dubai, UAE [AJF2018036]
  2. Research Institute of Medical and Health Sciences, University of Sharjah (UOS) [1901090159]
  3. Terry Fox Foundation
  4. Sharjah Research Academy
  5. University of Sharjah

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PRMT5, an important enzyme overexpressed in various cancers, particularly in colorectal cancer, is associated with disease progression and metastasis. Inhibitors targeting PRMT5 have shown promising anticancer effects in vitro, suggesting its potential as a biomarker for colorectal cancer diagnosis and prognosis.
Protein arginine N-methyltransferase 5 (PRMT5) enzyme is one of the eight canonical PRMTs, classified as a type II PRMT, induces arginine monomethylation and symmetric dimethylation. PRMT5 is known to be overexpressed in multiple cancer types, including colorectal cancer (CRC), where its overexpression is associated with poor survival. Recent studies have shown that upregulation of PRMT5 induces tumor growth and metastasis in CRC. Moreover, various novel PRMT5 inhibitors tested on CRC cell lines showed promising anticancer effects. Also, it was suggested that PRMT5 could be a valid biomarker for CRC diagnosis and prognosis. Hence, a deeper understanding of PRMT5-mediated CRC carcinogenesis could provide new avenues towards developing a targeted therapy. In this study, we started with in silico analysis correlating PRMT5 expression in CRC patients as a prelude to further our investigation of its role in CRC. We then carried out a comprehensive review of the scientific literature that dealt with the role(s) of PRMT5 in CRC pathogenesis, diagnosis, and prognosis. Also, we have summarized key findings from in vitro research using various therapeutic agents and strategies directly targeting PRMT5 or disrupting its function. In conclusion, PRMT5 seems to play a significant role in the pathogenesis of CRC; therefore, its prognostic and therapeutic potential merits further investigation.

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