Related Experiment Video

Updated: Jan 18, 2026

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
10:10

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries

Published on: March 31, 2019

8.7K

YTHDC1 orchestrates oncogenic splicing via the CLK1-SRSF1 splicing machinery to regulate castration-resistant

Parth Gupta1, Devesh Srivastava1, Vinayak Nayak1

  • 1Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502285, India.

Molecular and Cellular Biochemistry
|May 22, 2025
PubMed

Insights

Androgen receptor variant 7 (AR-V7) drives prostate cancer progression and enzalutamide resistance. Targeting YTHDC1 RNA-binding protein can restore enzalutamide sensitivity by reducing AR-V7 levels.

Area of Science:

  • Molecular Oncology
  • RNA Biology
  • Cancer Therapeutics

Background:

  • Androgen receptor variant 7 (AR-V7) is a key driver of castration-resistant prostate cancer (CRPC) progression.
  • AR-V7 expression confers resistance to anti-androgen therapies like enzalutamide.
  • Understanding AR-V7 regulation is crucial for developing novel CRPC treatments.

Purpose of the Study:

  • To investigate the role of RNA-binding protein YTHDC1 in regulating AR-V7 splicing.
  • To explore YTHDC1 as a potential therapeutic target for overcoming enzalutamide resistance in CRPC.

Main Methods:

  • Investigated YTHDC1 expression in CRPC samples.
  • Assessed the impact of modulating YTHDC1 expression on AR-V7 levels and enzalutamide sensitivity.
  • Elucidated the mechanism of YTHDC1-mediated AR-V7 splicing involving SRSF1 and CLK1.
  • Examined YTHDC1's regulation of other oncogenic transcripts.

Main Results:

  • YTHDC1 is overexpressed in CRPC and its modulation affects AR-V7 levels.
  • Targeting YTHDC1 restores enzalutamide sensitivity in CRPC cells.
  • YTHDC1 facilitates AR-V7 splicing by recruiting phosphorylated SRSF1 and modulating CLK1.
  • YTHDC1 also regulates other oncogenic transcripts like Bcl-2, Cyclin D1, Nova1, and VEGF-A.

Conclusions:

  • YTHDC1 plays a significant role in AR-V7 generation and CRPC progression.
  • Targeting YTHDC1 presents a novel therapeutic strategy to overcome AR-V7-mediated enzalutamide resistance in CRPC patients.
Keywords:
AR-V7Alternative splicingCLK1Castration-resistant prostate cancer (CRPC)YTHDC1

More Related Videos

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

13.3K
Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

15.4K

Related Concept Videos

Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.3K
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...
60.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
9.8K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.6K
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
3.9K