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Updated: Jul 21, 2025

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CDC20 Is Regulated by the Histone Methyltransferase, KMT5A, in Castration-Resistant Prostate Cancer

Zainab A H Alebady1,2, Mahsa Azizyan1, Sirintra Nakjang3

  • 1Biosciences Institute, Newcastle Cancer Centre, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Cancers
|July 29, 2023
PubMed

Insights

KMT5A acts as an oncogene in prostate cancer, regulating genes involved in apoptosis and DNA damage. Targeting KMT5A and its downstream target CDC20 shows therapeutic potential for prostate cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • KMT5A (methyltransferase) is implicated as an oncogene in prostate cancer.
  • Androgen receptor (AR) signaling is crucial in prostate cancer progression.
  • Identifying KMT5A's role under active AR is key for therapeutic strategies.

Purpose of the Study:

  • To investigate genes and cellular processes regulated by KMT5A in prostate cancer cells with an active androgen receptor.
  • To validate KMT5A as a therapeutic target and CDC20 as a potential biomarker.

Main Methods:

  • Microarray analysis of prostate cancer cell lines with KMT5A knockdown and active AR.
  • Bioinformatic analysis (KEGG pathway, Gene Ontology) of gene expression data.
  • Investigation of KMT5A's regulatory mechanism on CDC20, including histone methylation and p53 signaling.
  • Correlation analysis with clinical prostate cancer samples.

Main Results:

  • KMT5A knockdown altered expression of 709 genes, impacting apoptosis, DNA damage, protein folding, and RNA splicing.
  • CDC20 was identified as a key KMT5A-regulated gene, independent of AR.
  • KMT5A regulates CDC20 via methyltransferase activity, histone H4K20 methylation, and the p53 pathway.
  • Positive correlation between KMT5A and CDC20 expression in clinical prostate cancer samples.

Conclusions:

  • KMT5A is a validated therapeutic target for prostate cancer.
  • CDC20 is a potential biomarker for KMT5A-targeted therapies in prostate cancer.
  • Understanding KMT5A-CDC20 axis provides insights into prostate cancer pathogenesis and treatment.
Keywords:
CDC20KMT5Abiomarkerp53prostate cancer

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