Related Experiment Video

Updated: Aug 26, 2025

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

6.8K

RAD21 amplification epigenetically suppresses interferon signaling to promote immune evasion in ovarian cancer

Peng Deng1, Zining Wang1, Jinghong Chen1

  • 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.

The Journal of Clinical Investigation
|October 6, 2022
PubMed

Insights

RAD21 amplification in ovarian cancer (OV) suppresses immune response by inhibiting interferon signaling. Targeting RAD21 enhances immunotherapy effectiveness and boosts anti-tumor T cell activity, offering a new strategy for OV treatment.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Copy number alterations are key in ovarian cancer (OV) development, but their impact on immune evasion is unclear.
  • RAD21, a cohesin complex component, is frequently amplified in OV and may influence immune responses.

Purpose of the Study:

  • To investigate the role of RAD21 in OV immune evasion.
  • To identify the molecular mechanisms by which RAD21 modulates immune signaling.
  • To evaluate RAD21 as a potential therapeutic target and biomarker for immunotherapy in OV.

Main Methods:

  • Analysis of RAD21-regulated transcriptional programs.
  • Investigation of RAD21 interactions with YAP/TEAD4 and the NuRD complex.
  • Correlation analysis of RAD21 expression and interferon signature genes in clinical OV cohorts.
  • Assessment of RAD21 ablation effects on anti-PD-1 therapy efficacy in murine syngeneic tumor models.

Main Results:

  • RAD21 directly interacts with YAP/TEAD4 and recruits NuRD to suppress interferon (IFN) signaling.
  • RAD21 overexpression inversely correlates with IFN signature gene expression in OV patient data.
  • RAD21 ablation in mouse models enhanced anti-PD-1 efficacy, increasing intratumoral CD8+ T cell activity.

Conclusions:

  • A RAD21-YAP/TEAD4-NuRD corepressor complex mediates immune modulation in ovarian cancer.
  • RAD21 is identified as a novel regulator of immune evasion in OV.
  • This complex represents a potential target and biomarker for precision immunotherapy in ovarian cancer.
Keywords:
Cancer immunotherapyEpigeneticsGenetic instabilityImmunologyOncology

More Related Videos

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

2.8K
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence08:55

Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence

Published on: November 2, 2014

12.4K

Related Concept Videos

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...
3.9K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.9K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.7K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.2K
RNA Interference01:23

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.3K