ArticleNucleic acids research2023
MEN1 is a regulator of alternative splicing and prevents R-loop-induced genome instability through suppression of RNA polymerase II elongation.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- The Genomic Patterns of Well-Differentiated Pancreatic Neuroendocrine Tumors (NETs) Identify Sub-Sets for Rational Therapeutic Targeting.International journal of molecular sciences · 2026Article
- An Integrative RNA Spliceosomic Landscape of Pancreatic Neuroendocrine Tumors Identifies Clinically Relevant Molecular Subgroups.Endocrine pathology · 2026Article
- Multi-omics dissection of R-loop dynamics in tumorigenesis: From transcription-replication conflict to therapeutic targets.Molecular therapy. Oncology · 2026Review
- An integrated analysis of MEN1 reveals its associations with clinical outcomes, cellular pathways, and the immune microenvironment.World journal of surgical oncology · 2026Article
- Integrative Analysis Reveals Conserved R-Loop Features in Mouse Embryonic Stem Cells.Epigenomes · 2026Article
- Regulation of R-Loop Dynamics by Proteins and Long Noncoding RNAs: An Emerging Paradigm for Cancer Treatment.Cancer science · 2026Review
- LSD1 maintains oocyte quality by epigenetically repressing CAMK2β to control granulosa cell-oocyte communication.Journal of translational medicine · 2026Article
- DOT1L activity limits transcription elongation velocity and favors RNAPII pausing to facilitate mutagenesis by AID.Nature communications · 2026Article
- MEN1 Promotes Ferroptosis by Disrupting CD44 Alternative Splicing to Suppress Lung Cancer.Cancer research · 2026Article
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Alternative splicing: from tumorigenesis to neoantigen-mediated cancer immunotherapy.Biomarker research · 2025Review
- aGenome-scale activation screen reveals lncRNA HNF1A-AS1 promotes pancreatic cancer metastasis through interacting with U2SURP to increase CD44 alternative splicing.Journal of gastroenterology · 2025Article
- Liquid biopsy diagnostics for non-small cell lung cancer via elucidation of tRNA signatures.Communications medicine · 2025Article
- The relevance of RNA-DNA interactions as regulators of physiological functions.Pflugers Archiv : European journal of physiology · 2025Review
- Impaired splicing machinery in craniopharyngiomas unveils PRPF8 and RAVER1 as novel biomarkers and therapeutic targets.Acta neuropathologica communications · 2025Article
- R-loops and small RNA regulatory interactions: mechanisms and clinical perspectives.Frontiers in cell and developmental biology · 2025Review
- Comparative Targeted Genome Profiling between Solid and Liquid Biopsies in Gastroenteropancreatic Neuroendocrine Neoplasms: A Proof-of-Concept Pilot Study.Neuroendocrinology · 2025Article
- Ion channel Piezo1 induces ferroptosis of trabecular meshwork cells: a novel observation in the pathogenesis in primary open angle glaucoma.American journal of physiology. Cell physiology · 2024Article
- Menin in Cancer.Genes · 2024Review
- A multi-tissue, splicing-based joint transcriptome-wide association study identifies susceptibility genes for breast cancer.American journal of human genetics · 2024Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The fidelity of alternative splicing (AS) patterns is essential for growth development and cell fate determination. However, the scope of the molecular switches that regulate AS remains largely unexplored. Here we show that MEN1 is a previously unknown splicing regulatory factor. MEN1 deletion resulted in reprogramming of AS patterns in mouse lung tissue and human lung cancer cells, suggesting that MEN1 has a general function in regulating alternative precursor mRNA splicing. MEN1 altered exon skipping and the abundance of mRNA splicing isoforms of certain genes with suboptimal splice sites. Chromatin immunoprecipitation and chromosome walking assays revealed that MEN1 favored the accumulation of RNA polymerase II (Pol II) in regions encoding variant exons. Our data suggest that MEN1 regulates AS by slowing the Pol II elongation rate and that defects in these processes trigger R-loop formation, DNA damage accumulation and genome instability. Furthermore, we identified 28 MEN1-regulated exon-skipping events in lung cancer cells that were closely correlated with survival in patients with lung adenocarcinoma, and MEN1 deficiency sensitized lung cancer cells to splicing inhibitors. Collectively, these findings led to the identification of a novel biological role for menin in maintaining AS homeostasis and link this role to the regulation of cancer cell behavior.
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