Related Experiment Video

Updated: Jun 13, 2025

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
07:22

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells

Published on: March 28, 2013

38.7K

PPARγ and C/EBPα enable adipocyte differentiation upon inhibition of histone methyltransferase PRC2 in malignant

Jiaqi Zhao1, Hui Qian2, Yang An1

  • 1Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

The Journal of Biological Chemistry
|September 14, 2024
PubMed

Insights

Inhibition of Polycomb repressive complex 2 (PRC2) promotes adipocyte differentiation in cancers by upregulating PPARG and CEBPA. This epigenetic mechanism offers potential for differentiation therapy in malignant rhabdoid tumors and sarcomas.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Cellular Differentiation

Background:

  • Loss of terminal differentiation is a key feature of cancer.
  • Polycomb repressive complex 2 (PRC2) regulates histone methylation and gene expression.
  • PRC2 inhibitors are being explored for cancer therapy, but mechanisms are unclear.

Purpose of the Study:

  • To investigate the role of PRC2 in adipocyte differentiation.
  • To elucidate the epigenetic mechanisms underlying PRC2-mediated gene regulation in cancer.
  • To explore the therapeutic potential of targeting PRC2 for differentiation therapy.

Main Methods:

  • Inhibition and depletion of PRC2 in malignant rhabdoid tumors and mesenchymal stem cells.
  • Analysis of gene expression for peroxisome proliferator-activated receptor gamma (PPARG) and CEBPA.
  • Histone H3K27 methylation analysis and gene knockout studies.
  • Combination therapy studies with a PRC2 inhibitor and a PPARγ agonist in xenograft models.
  • Correlation analysis with patient prognosis data from The Cancer Genome Atlas.

Main Results:

  • PRC2 inhibition or depletion enhanced adipocyte differentiation by upregulating PPARG and CEBPA.
  • PRC2 directly represses PPARG and CEBPA transcription via H3K27 methylation.
  • Knockout of PPARG impaired C/EBPα expression and adipocyte differentiation.
  • Combination therapy showed enhanced tumor growth inhibition.
  • High CEBPA, PLIN1, and FABP4 levels correlated with better prognosis in sarcoma patients.

Conclusions:

  • PRC2 epigenetically regulates PPARG and CEBPA, crucial for adipocyte differentiation.
  • Targeting PRC2, potentially in combination with PPARγ agonists, shows therapeutic promise for sarcomas and malignant rhabdoid tumors.
  • This study reveals a novel epigenetic mechanism for differentiation therapy.
Keywords:
C/EBPα sarcomaPPARγPRC2 inhibitorsadipocyte differentiation

More Related Videos

Dual Effects of Melanoma Cell-derived Factors on Bone Marrow Adipocytes Differentiation07:00

Dual Effects of Melanoma Cell-derived Factors on Bone Marrow Adipocytes Differentiation

Published on: August 23, 2018

6.2K
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

15.0K

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...
4.5K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.5K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
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...
3.8K
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...
3.4K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.2K