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CDC20 is regulated by the histone methyltransferase, KMT5A, in castration resistant prostate cancer

Alebady, Zainab A H, Azizyan, Mahsa, Nakjang, Sirintra, Lishman-Walker, Emma, Al-Kharaif, Dhuha, Choo, Hui Xian, Garnham, Rebecca, Scott, Emma, Johnson, Katya L, Robson, Craig N and Coffey, Kelly (2023) CDC20 is regulated by the histone methyltransferase, KMT5A, in castration resistant prostate cancer.

Item Type: Article


The methyltransferase, KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis we have performed a microarray study in a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced. KEGG pathway and Gene Ontology analysis revealed apoptosis and DNA damage signal- ing are up-regulated in response to KMT5A knockdown whilst protein folding and RNA splicing were down-regulated. Under these conditions, the top non-AR regulated gene was found to be CDC20, a key regulator of the spindle assembly checkpoint with an oncogenic role in several cancer types. Further investigation revealed that KMT5A regulates CDC20 in a methyltransferase depend- ent manner to modulate both histone H4K20 methylation within its promoter region and indirectly via the p53 signalling pathway. A positive correlation between KMT5A and CDC20 expression was also observed in clinical prostate cancer samples further supporting this association. Therefore, we conclude that KMT5A is a valid therapeutic target for the treatment of prostate cancer and CDC20 could potentially be utilized as a biomarker for effective therapeutic targeting.

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Depositing User: Rebecca Garnham


Item ID: 17663
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Date Deposited: 03 Jul 2024 09:13
Last Modified: 03 Jul 2024 09:13


Author: Zainab A H Alebady
Author: Mahsa Azizyan
Author: Sirintra Nakjang
Author: Emma Lishman-Walker
Author: Dhuha Al-Kharaif
Author: Hui Xian Choo
Author: Rebecca Garnham
Author: Emma Scott
Author: Katya L Johnson
Author: Craig N Robson
Author: Kelly Coffey

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine


Sciences > Biomedical Sciences
Sciences > Health Sciences

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