Related Experiment Video

Updated: Aug 20, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

9.0K

MYC regulates a pan-cancer network of co-expressed oncogenic splicing factors

Laura Urbanski1, Mattia Brugiolo2, SungHee Park2

  • 1The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; Graduate Program in Genetics and Development, UConn Health, Farmington, CT, USA.

Cell Reports
|November 23, 2022
PubMed

Insights

MYC drives cancer by altering gene splicing. Researchers identified a splicing factor module linked to MYC activity across many cancers, offering new therapeutic targets for MYC-driven tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genomics

Background:

  • MYC oncoprotein dysregulation is common in cancer (>50%) but direct MYC targeting has failed.
  • MYC influences alternative mRNA splicing, a mechanism underexplored in cancer.
  • Targeting downstream MYC effector pathways is a promising therapeutic strategy.

Purpose of the Study:

  • To investigate the mechanistic links between MYC and mRNA splicing machinery in cancer.
  • To identify splicing factor modules (SF-modules) associated with MYC activity in tumors.
  • To explore the therapeutic potential of targeting MYC-regulated splicing.

Main Methods:

  • Identification of co-expressed SF-modules in MYC-active breast tumors.
  • Correlation analysis of SF-modules with MYC activity across 33 tumor types.
  • Functional studies in mammary cell models and breast cancer organoids.
  • Analysis of a pan-cancer splicing signature for survival correlation.

Main Results:

  • A pan-cancer SF-module correlating with MYC activity was identified.
  • MYC activation in mammary cells caused co-upregulation of SF-module members and altered >4,000 splicing events.
  • Overexpression of the SF-module in breast cancer organoids mimicked MYC-regulated splicing, increasing organoid size and invasiveness.
  • Knockdown of the SF-module reduced organoid size.

Conclusions:

  • MYC activation drives a specific splicing program through co-regulated splicing factors.
  • This MYC-driven splicing signature is conserved across multiple cancer types and impacts tumor progression.
  • The identified SF-modules and splicing signature represent potential therapeutic targets and biomarkers for MYC-driven cancers.
Keywords:
CP: CancerMYCRNA splicingSR proteinsalternative splicingbreast cancercancerco-expression analysisco-expression modulesoncogenesorganoidspan-cancersplicing factors

More Related Videos

Using the E1A Minigene Tool to Study mRNA Splicing Changes10:25

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

5.0K
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

2.8K

Related Concept Videos

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...
4.3K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

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...
9.1K
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...
4.6K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
976
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
23.0K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.4K