Related Experiment Video

Updated: Aug 28, 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

6.9K

Androgen Receptor Splice Variants Contribute to the Upregulation of DNA Repair in Prostate Cancer

Yuri Tolkach1,2, Anika Kremer1, Gábor Lotz3

  • 1Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany.

Cancers
|September 23, 2022
PubMed
Abstract

Insights

Androgen receptor splice variants (AR-Vs) in prostate cancer (PCA) increase DNA repair activity. This may explain why PARP inhibition is less effective in patients with AR-Vs, suggesting AR-Vs as potential biomarkers for therapy response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Canonical androgen receptor (AR) signaling influences DNA repair genes in prostate cancer (PCA).
  • Androgen deprivation therapy (ADT) can suppress DNA repair and create synthetic lethality with PARP inhibition.
  • AR splice variants (AR-Vs) are prevalent in advanced PCA and may alter DNA repair.

Purpose of the Study:

  • To investigate the impact of AR splice variants (AR-Vs) on DNA repair machinery in prostate cancer.
  • To correlate AR-V expression with AR pathway activity and DNA repair gene expression.
  • To evaluate the role of AR-Vs in therapeutic response, particularly with PARP inhibition.

Main Methods:

  • Analysis of 273 prostate cancer tissue samples (hormone-naïve, metastatic, ADT-treated, castration-refractory PCA).
  • Profiling of target gene transcript levels using the nCounter platform.
  • Experimental validation in AR/AR-V7-expressing LNCaP cells subjected to ionizing radiation.

Main Results:

  • AR-Vs were detected in 50% of ADT-treated PCAs and 67% of castration-refractory PCAs (CRPCs).
  • AR-V presence strongly correlated with heightened AR pathway activity and DNA repair gene expression.
  • AR-V-expressing CRPCs showed a 2.5-fold increase in DNA repair scores compared to AR-V-negative samples.

Conclusions:

  • AR splice variants, like AR-V7, in prostate cancer patients undergoing ADT may reduce the efficacy of PARP inhibition by modulating DNA repair gene expression.
  • AR-Vs could be responsible for diminished or absent therapeutic effects in patients receiving PARP inhibitors.
  • AR-Vs warrant further investigation as predictive biomarkers for therapy response in prostate cancer.
Keywords:
AR-V7BRCA1BRCA2DNA repairandrogen deprivation therapyandrogen receptorcastration-refractory prostate cancerprostate cancersplice variant

More Related Videos

MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR08:30

MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR

Published on: May 16, 2012

24.6K
Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models09:58

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

Published on: December 9, 2016

13.8K

Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.7K
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.7K
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.6K
Overview of DNA Repair02:25

Overview of DNA Repair

7.7K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.3K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.1K