Related Experiment Video

Updated: Dec 4, 2025

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
10:44

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

Published on: May 5, 2023

1.7K

Endogenous retroviruses drive KRAB zinc-finger protein family expression for tumor suppression

Jumpei Ito1, Izumi Kimura1, Andrew Soper2

  • 1Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 1088639, Japan.

Science Advances
|October 22, 2020
PubMed

Insights

Human endogenous retroviruses (HERVs) activation in tumors up-regulates Krüppel-associated box domain-containing zinc-finger family proteins (KZFPs), which are linked to better disease outcomes and tumor suppression.

Area of Science:

  • Genomics
  • Cancer Biology
  • Epigenetics

Background:

  • Gene expression aberrations are characteristic of cancer, but their underlying mechanisms are not fully understood.
  • Human endogenous retroviruses (HERVs) are repetitive genomic elements that can function as enhancers.
  • Epigenetic activation of HERVs in tumors suggests a potential role in global gene expression changes.

Purpose of the Study:

  • To investigate the role of HERV activation in driving gene expression aberrations in cancer.
  • To identify specific genes regulated by activated HERVs in tumor cells.
  • To explore the functional consequences of HERV-driven gene expression changes on cancer progression.

Main Methods:

  • Analysis of gene expression data in tumor samples.
  • Identification of HERVs and their proximity to other genes.
  • Correlation analysis between HERV activation, gene expression, and clinical outcomes.

Main Results:

  • HERV activation in tumors leads to the upregulation of hundreds of Krüppel-associated box domain-containing zinc-finger family proteins (KZFPs).
  • KZFP genes are located near activated HERVs and are transcriptionally regulated by them.
  • Increased HERV and KZFP expression in tumors correlated with improved disease conditions.

Conclusions:

  • HERV activation in tumors drives coordinated upregulation of KZFPs.
  • Increased KZFP expression alters cell cycle and cell-matrix adhesion genes, suppressing cancer cell growth, migration, and invasion.
  • HERV-driven KZFP elevation suggests a tumor-suppressive mechanism in cancer.

More Related Videos

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy08:51

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy

Published on: April 3, 2018

9.4K
Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

2.6K

Related Concept Videos

Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
6.5K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
12.8K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
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...
9.0K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.5K
LTR Retrotransposons03:08

LTR Retrotransposons

LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
19.0K