The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer.

TitleThe METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer.
Publication TypeJournal Article
Year of Publication2022
AuthorsHaigh DB, Woodcock CL, Lothion-Roy J, Harris AE, Metzler VM, Persson JL, Robinson BD, Khani F, Alsaleem M, Ntekim A, Madhusudan S, Davis MB, Laursen KB, Gudas LJ, Rutland CS, Toss MS, Archer N, Bodi Z, Rakha EA, Fray RG, Jeyapalan JN, Mongan NP
JournalCancers (Basel)
Date Published2022 Oct 20

Prostate cancer (PCa) is a leading cause of cancer-related deaths and is driven by aberrant androgen receptor (AR) signalling. For this reason, androgen deprivation therapies (ADTs) that suppress androgen-induced PCa progression either by preventing androgen biosynthesis or via AR signalling inhibition (ARSi) are common treatments. The N6-methyladenosine (m6A) RNA modification is involved in regulating mRNA expression, translation, and alternative splicing, and through these mechanisms has been implicated in cancer development and progression. RNA-m6A is dynamically regulated by the METTL3 RNA methyltransferase complex and the FTO and ALKBH5 demethylases. While there is evidence supporting a role for aberrant METTL3 in many cancer types, including localised PCa, the wider contribution of METTL3, and by inference m6A, in androgen signalling in PCa remains poorly understood. Therefore, the aim of this study was to investigate the expression of METTL3 in PCa patients and study the clinical and functional relevance of METTL3 in PCa. It was found that METTL3 is aberrantly expressed in PCa patient samples and that siRNA-mediated METTL3 knockdown or METTL3-pharmacological inhibition significantly alters the basal and androgen-regulated transcriptome in PCa, which supports targeting m6A as a novel approach to modulate androgen signalling in PCa.

Alternate JournalCancers (Basel)
PubMed ID36291932
PubMed Central IDPMC9600477
Grant ListBB/M008770/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
MRF-157-0021-F-NTEKI / / Medical Research Foundation-African Research Excellence Fund /
20CHAL04 / / Prostate Cancer Foundation and the John Black Charitable foundation /
Not applicable / / Stanyard Family Donation /
Related Faculty: 
Brian Robinson, M.D. Francesca Khani, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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