Related Experiment Video

Updated: Jan 30, 2026

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

8.9K

The Transcriptional Regulator Sin3A Contributes to the Oncogenic Potential of STAT3

Giovanni Gambi1, Elisabetta Di Simone1, Veronica Basso1

  • 1Division of Immunology, Transplantation and Infectious Disease, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Cancer Research
|January 30, 2019
PubMed

Insights

Oncogene-driven STAT3 acetylation, mediated by the Sin3A complex, silences tumor suppressor genes in cancer. Targeting this STAT3/Sin3A axis offers a new therapeutic strategy for STAT3-addicted tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Malignant cells frequently exhibit epigenetic silencing of key gene regulatory regions.
  • Aberrant activation of Signal Transducer and Activator of Transcription 3 (STAT3) is common in various cancers.
  • The precise mechanisms by which STAT3's constitutive acetylation leads to tumor suppressor gene (TSG) repression remain unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying STAT3-mediated transcriptional repression in cancer.
  • To identify novel therapeutic targets for STAT3-dependent malignancies.

Main Methods:

  • Utilized NPM-ALK+ anaplastic large-cell lymphoma (ALCL) as a model system.
  • Employed patient-derived tumor xenografts for in vivo validation.
  • Investigated the role of STAT3 acetylation, PI3K/mTORC1 signaling, resveratrol treatment, and STAT3-Sin3A complex interactions.

Main Results:

  • Constitutive STAT3 acetylation, driven by ALK activity, was observed in ALCL cells and xenografts.
  • Resveratrol treatment reduced STAT3 acetylation, restored TSG expression, and induced apoptosis.
  • STAT3 constitutively interacts with the Sin3A repressor complex, binding to silenced TSG promoters in a resveratrol-sensitive manner.
  • Silencing SIN3A reactivated TSG, induced apoptosis, and reduced tumorigenicity.
  • A similar STAT3-Sin3A interaction was identified in breast adenocarcinoma cells, crucial for TSG silencing and survival.

Conclusions:

  • Oncogene-driven STAT3 acetylation and its constitutive association with Sin3A are key contributors to STAT3's oncogenic activity.
  • The Sin3A complex acts as a mediator of STAT3's transcriptional repressor function.
  • The STAT3/Sin3A axis represents a druggable target for treating STAT3-addicted cancers.

More Related Videos

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

3.1K
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

15.5K

Related Concept Videos

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...
7.8K
Master Transcription Regulators02:23

Master Transcription Regulators

2.8K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.3K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

2.6K
Transcriptional Regulation: Riboswitches01:23

Transcriptional Regulation: Riboswitches

Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
686
Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.7K