Related Experiment Video

Updated: Oct 26, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
12:13

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

7.0K

Histone acetyltransferase 1 upregulates androgen receptor expression to modulate CRPC cell resistance to enzalutamide

Zhe Hong1, Zhendong Xiang1, Pan Zhang2

  • 1Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

Clinical and Translational Medicine
|July 29, 2021
PubMed

Insights

Histone acetyltransferase 1 (HAT1) overexpression drives castration-resistant prostate cancer (CRPC) progression and enzalutamide (ENZ) resistance. Targeting HAT1 may restore sensitivity to ENZ in CRPC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Castration-resistant prostate cancer (CRPC) presents limited treatment options, especially after failure of next-generation androgen deprivation therapy (ADT) drugs like enzalutamide (ENZ).
  • The androgen receptor (AR) is crucial in prostate cancer (PCa) and CRPC progression and drug resistance.
  • The role of Histone acetyltransferase 1 (HAT1) in CRPC and its relationship with AR signaling remain unclear.

Purpose of the Study:

  • To investigate the role of HAT1 in CRPC progression and enzalutamide resistance.
  • To elucidate the relationship between HAT1 and androgen receptor (AR) signaling in prostate cancer.
  • To explore HAT1 as a potential therapeutic target for CRPC.

Main Methods:

  • Assessed HAT1 expression in PCa cells and correlated it with CRPC progression and AR expression (AR-FL, AR-V7).
  • Investigated the involvement of the BRD4-mediated pathway in HAT1-AR regulation.
  • Evaluated the effect of HAT1 knockdown and ascorbate treatment on CRPC cell response to ENZ in vitro and in vivo mouse models.

Main Results:

  • HAT1 is highly expressed in PCa cells, with overexpression linked to CRPC cell proliferation.
  • HAT1 expression positively correlates with both full-length AR (AR-FL) and variant 7 (AR-V7) expression, mediated by BRD4.
  • Knockdown of HAT1 resensitized CRPC cells to ENZ treatment; ascorbate decreased AR expression by downregulating HAT1.

Conclusions:

  • HAT1 is a critical oncoprotein in prostate cancer and castration-resistant prostate cancer.
  • A novel AR signaling regulation pathway involving HAT1 and BRD4 in PCa and CRPC was identified.
  • HAT1 represents a promising therapeutic target for overcoming enzalutamide resistance in CRPC patients.
Keywords:
androgen receptorbromodomain containing protein 4castration-resistant prostate cancerenzalutamidehistone acetyltransferase 1

More Related Videos

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses08:36

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses

Published on: October 24, 2019

11.4K
Serum and Plasma Copy Number Detection Using Real-time PCR09:21

Serum and Plasma Copy Number Detection Using Real-time PCR

Published on: December 15, 2017

11.6K

Related Concept Videos

Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.9K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.0K
Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
4.1K
Testosterone: Functions and Regulation01:26

Testosterone: Functions and Regulation

The intricate hormonal interplay essential for male reproductive health begins with the release of gonadotropin-releasing hormone (GnRH) by the hypothalamus. This hormone prompts the pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). LH targets the Leydig cells in the testes, stimulating them to produce and release testosterone. In concert with testosterone, FSH acts on the Sertoli cells within the seminiferous tubules to facilitate the release of...
1.3K