Related Experiment Video
Updated: Sep 1, 2025
10:06
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
9.0K
A widespread length-dependent splicing dysregulation in cancer
Sirui Zhang1, Miaowei Mao1, Yuesheng Lv2
1CAS Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Science Advances
|August 17, 2022
Summary
Cancer exhibits altered splicing, particularly excluding short exons. These cancer-associated short exons (CASEs) can predict survival and offer new diagnostic and therapeutic strategies.
Area of Science:
- Molecular biology
- Genomics
- Cancer research
Background:
- Alternative splicing dysregulation is a hallmark of cancer.
- Common features and mechanisms of cancer splicing alterations are not fully understood.
Purpose of the Study:
- To investigate length-dependent splicing regulation in cancer.
- To identify common features of cancer-associated splicing events.
- To develop clinical applications based on splicing alterations.
Main Methods:
- Systematic transcriptome analysis of thousands of cancer patients.
- Identification and characterization of cancer-associated short exons (CASEs).
- Development of a CASE-based panel for cancer stratification and survival prediction.
Main Results:
- Short exons are preferentially mis-spliced and excluded in cancers.
- CASEs are conserved, encode low-complexity peptides, and are enriched in GTPase regulators and cell adhesion.
- A CASE-based panel demonstrated reliable cancer stratification and survival prediction.
- CASE mis-splicing is linked to elevated transcription and altered RNA binding proteins.
Conclusions:
- A common, length-dependent splicing dysregulation pattern exists in cancer.
- CASEs serve as potential biomarkers for cancer diagnosis, stratification, and prognosis.
- Understanding CASE regulation offers new therapeutic avenues for cancer treatment.
Related Concept Videos
01:32RNA Splicing
56.7K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.7K
02:18Alternative RNA Splicing
21.6K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.6K
02:41Chromatin Structure Regulates pre-mRNA Processing
7.1K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.1K
01:12Loss of Tumor Suppressor Gene Functions
5.1K
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...
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...
5.1K
02:21Cancers Originate from Somatic Mutations in a Single Cell
12.5K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
12.5K
01:36Pre-mRNA Processing: RNA Splicing
5.4K
5.4K