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Updated: Jan 13, 2026
10:06
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
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Splicing factor FUS facilitates the progression of PIT1-lineage PitNETs by upregulating MDM2.
Xu Wang1,2,3, Jiang Li1,2, Chenggang Jiang1,2
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Theranostics
|January 9, 2026
Summary
Splicing factor FUS promotes pituitary tumor growth by regulating MDM2 splicing. Targeting this process with antisense oligonucleotides halts tumor progression, offering a new therapeutic strategy for PIT1-lineage pituitary neuroendocrine tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Splicing factors are crucial in mRNA processing and linked to tumor progression.
- Aberrant splicing factor expression correlates with pituitary neuroendocrine tumor (PitNET) invasiveness.
- This study investigates splicing factors in PIT1-lineage PitNET progression.
Purpose of the Study:
- To explore the role of splicing factors in PIT1-lineage PitNET progression.
- To assess targeting splicing as a therapeutic strategy for PitNETs.
- To elucidate the function of FUS in PitNET development.
Main Methods:
- Gene expression analysis on 40 clinical PitNET samples.
- Transcriptome and RNA immunoprecipitation sequencing (RIP-seq) to study FUS-mediated splicing.
- Minigene assays, Annexin V/PI, and JC-1 staining to validate splicing and apoptosis.
Main Results:
- Elevated FUS expression in PIT1-lineage PitNETs correlated with higher proliferation and lower apoptosis.
- FUS knockdown induced exon skipping and activated the p53 pathway.
- FUS promotes MDM2 full-length transcript via exon 3 inclusion, inhibiting p53.
Conclusions:
- FUS is a critical splicing factor in PitNET progression.
- Targeting FUS-mediated MDM2 splicing can restore p53 levels and impede PitNET growth.
- This presents a novel therapeutic strategy for PIT1-lineage PitNETs.
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