ArticleMolecular cancer2022
AP4 suppresses DNA damage, chromosomal instability and senescence via inducing MDC1/Mediator of DNA damage Checkpoint 1 and repressing MIR22HG/miR-22-3p.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Non-coding RNAs participate in interactions between senescence and gastrointestinal cancers.Frontiers in genetics · 2024Pooled it
- Review
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- Transcription Activation of DEPDC1B Upon EBF1 Loss Contributes to Cell Cycle Progression and Epithelial-Mesenchymal Transition in Colon Adenocarcinoma.Biochemical genetics · 2026Article
- Decoding the Spatiotemporal Logic of Cellular Senescence through Multimodal Exosomal miRNA Integration.JACS Au · 2026Article
- Molecular mechanisms of 5-FU resistance in colorectal cancer: the regulatory role of lncRNAs.Journal of cancer research and clinical oncology · 2026Review
- PARG inhibition in ATM-deficient prostate cancer: from mechanistic discovery to therapeutic potential.Journal of translational medicine · 2026Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- Ononin Sensitizes Papillary Thyroid Carcinoma Cells to Cisplatin by Repressing DNA Damage Response via E2F2.International journal of endocrinology · 2026Article
- Systematic profiling reveals distinct senescence signatures and regulators across human brain cell types.Nature communications · 2025Article
- Long Non-coding RNA MIR22HG Alleviates Ischemic Acute Kidney Injury by Targeting the miR-134-5p/NFAT5 axis.Inflammation · 2025Article
- Balancing between cuproplasia and copper-dependent cell death: molecular basis and clinical implications of ATOX1 in cancer.Journal of experimental & clinical cancer research : CR · 2025Review
- DNA methylation protects cancer cells against senescence.Nature communications · 2025Article
- Genetic targets related to aging for the treatment of coronary artery disease.BMC medical genomics · 2025Article
- SLC30A4-AS1 Mediates the Senescence of Periodontal Ligament Stem Cells in Inflammatory Environments via the Alternative Splicing of TP53BP1.Cell proliferation · 2025Article
- HDGF Knockout Suppresses Colorectal Cancer Progression and Drug Resistance by Modulating the DNA Damage Response.Biomolecules · 2025Article
- Review
- Regulatory Network Inference of Induced Senescent Midbrain Cell Types Reveals Cell Type-Specific Senescence-Associated Transcriptional Regulators.bioRxiv : the preprint server for biology · 2025Article
- Review of the Different Outcomes Produced by Genetic Knock Out of the Long Non-coding microRNA-host-gene MIR22HGMicroRNA (Shariqah, United Arab Emirates) · 2025Review
- Chromosomal instability is associated with prognosis and efficacy of bevacizumab after resection of colorectal cancer liver metastasis.Annals of medicine · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAP4 (TFAP4) encodes a basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor and is a direct target gene of the oncogenic transcription factor c-MYC. Here, we set out to determine the relevance of AP4 in human colorectal cancer (CRC) cells.
methodsA CRISPR/Cas9 approach was employed to generate AP4-deficient CRC cell lines with inducible expression of c-MYC. Colony formation, β-gal staining, immunofluorescence, comet and homologous recombination (HR) assays and RNA-Seq analysis were used to determine the effects of AP4 inactivation. qPCR and qChIP analyses was performed to validate differentially expressed AP4 targets. Expression data from CRC cohorts was subjected to bioinformatics analyses. Immunohistochemistry was used to evaluate AP4 targets in vivo. Ap4-deficient APC
resultsInactivation of AP4 in CRC cell lines resulted in increased spontaneous and c-MYC-induced DNA damage, chromosomal instability (CIN) and cellular senescence. AP4-deficient cells displayed increased expression of the long non-coding RNA MIR22HG, which encodes miR-22-3p and was directly repressed by AP4. Furthermore, Mediator of DNA damage Checkpoint 1 (MDC1), a central component of the DNA damage response and a known target of miR-22-3p, displayed decreased expression in AP4-deficient cells. Accordingly, MDC1 was directly induced by AP4 and indirectly by AP4-mediated repression of miR-22-3p. Adenomas and organoids from Ap4-deficient APC
conclusionsIn summary, AP4, miR-22-3p and MDC1 form a conserved and coherent, regulatory feed-forward loop to promote DNA repair, which suppresses DNA damage, senescence and CIN, and contributes to 5-FU resistance. These findings explain how elevated AP4 expression contributes to development and chemo-resistance of colorectal cancer after c-MYC activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.