Related Experiment Video

Updated: Nov 10, 2025

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

8.7K

MLL3 suppresses tumorigenesis through regulating TNS3 enhancer activity

Jun-Yi Zheng1,2, Chen-Yu Wang1,2, Chuan Gao1,2

  • 1Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, Hubei, 430072, China.

Cell Death & Disease
|April 7, 2021
PubMed

Insights

The MLL3 enzyme suppresses cancer by regulating TNS3 expression. MLL3 depletion enhances cancer cell migration, revealing a new therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • MLL3 (histone H3K4 methyltransferase) is frequently mutated in cancer.
  • The molecular mechanisms of MLL3's role in cancer are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which MLL3 suppresses cancer.
  • To identify MLL3 target genes and their role in cancer cell migration and proliferation.

Main Methods:

  • CRISPR/sgRNA for MLL3 depletion.
  • RNA-Sequencing (RNA-Seq) and Chromatin Immunoprecipitation Sequencing (ChIP-Seq) to identify MLL3 targets.
  • 3C assay to confirm enhancer-promoter interaction.
  • dCas9-KRAB system for enhancer repression.
  • Exogenous TNS3 expression in MLL3-deficient cells.

Main Results:

  • MLL3 depletion enhanced cancer cell migration but not proliferation.
  • TNS3 was identified as a direct MLL3 target gene.
  • MLL3 regulates H3K4me1 and H3K27ac marks on a TNS3 enhancer.
  • Enhancer-promoter interaction and enhancer activity are crucial for TNS3 expression.
  • TNS3 expression reversed the enhanced migration phenotype in MLL3-deficient cells.

Conclusions:

  • MLL3 suppresses cancer progression by maintaining TNS3 expression via epigenetic regulation of its enhancer.
  • This study reveals a novel mechanism of MLL3 tumor suppression.
  • MLL3 and TNS3 represent potential targets for cancer diagnosis and drug development.

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

2.9K
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

1.9K

Related Concept Videos

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...
4.8K
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...
8.5K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.4K
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
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.8K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
22.8K