Related Experiment Video
Updated: Aug 1, 2025
10:25
Using the E1A Minigene Tool to Study mRNA Splicing Changes
Published on: April 22, 2021
5.0K
Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer
Ledong Wan1, Kuan-Ting Lin1, Mohammad Alinoor Rahman1
1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Cancer Discovery
|April 26, 2023
Summary
The splicing factor SRSF1 promotes pancreatitis and pancreatic cancer (PDAC) by activating MAPK signaling. Its downregulation normally maintains pancreas cell homeostasis, but this feedback is overcome during PDAC development.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- Inflammation is linked to pancreatic ductal adenocarcinoma (PDAC).
- The role of RNA splicing factors in pancreatitis and PDAC is unclear.
- SRSF1 is a splicing factor implicated in tumorigenesis.
Purpose of the Study:
- To investigate the role of SRSF1 in pancreatitis and PDAC.
- To elucidate the mechanisms by which SRSF1 influences these conditions.
Main Methods:
- Analysis of SRSF1 expression in pancreatitis, PDAC precursor lesions, and tumors.
- Investigating SRSF1's effect on MAPK signaling and IL1R1 expression.
- Studying SRSF1 feedback regulation in KRASG12D-expressing cells and organoids.
Main Results:
- SRSF1 is highly expressed in pancreatitis and PDAC.
- Increased SRSF1 induces pancreatitis and accelerates KRASG12D-driven PDAC.
- SRSF1 upregulates IL1R1, activating MAPK signaling.
- Negative feedback downregulates SRSF1 in normal KRASG12D cells, but MYC overcomes this in PDAC.
Conclusions:
- SRSF1 plays a critical role in the development of pancreatitis and PDAC.
- Dysregulated SRSF1-mediated alternative splicing is a potential therapeutic target for PDAC.
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