ArticleJournal of experimental & clinical cancer research : CR2021
Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Circadian Disruption as a Determinant of the Tumor Temporal State in Colorectal Cancer: A PRISMA-Based Systematic Review Integrating Metabolism, Immunity, and Metastasis.International journal of molecular sciences · 2026Pooled it
- Role of capsaicin, circadian clock genes, and TRPV1 in colorectal carcinogenesis: Lessons and future directions.Journal of advanced research · 2026Review
- Circadian Clock Genes in Colorectal Cancer: From Molecular Mechanisms to Chronotherapeutic Applications.Biomedicines · 2026Review
- TIMELESS Promotes LUAD Growth via Suppressing Transferrin-Mediated Ferroptosis and Reprograms the Tumor Microenvironment against Anti-PD-1 Immunotherapy.Cancer communications (London, England) · 2026Article
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- Circadian rhythm in gastrointestinal cancer: clinical applications and future perspectives.Annals of medicine · 2025Review
- TIMELESS as a prognostic biomarker and therapeutic target in gastric cancer.Journal, genetic engineering & biotechnology · 2025Article
- Epigenetic marvels: exploring the landscape of colorectal cancer treatment through cutting-edge epigenetic-based drug strategies.Clinical epigenetics · 2025Review
- The Common Hallmarks and Interconnected Pathways of Aging, Circadian Rhythms, and Cancer: Implications for Therapeutic Strategies.Research (Washington, D.C.) · 2025Review
- Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Non-Muscle Myosin II A: Friend or Foe in Cancer?International journal of molecular sciences · 2024Review
- Unveiling the enigmatic role of MYH9 in tumor biology: a comprehensive review.Cell communication and signaling : CCS · 2024Review
- Identification of diagnostic markers related to inflammatory response and cellular senescence in endometriosis using machine learning and in vitro experiment.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- The Circadian Clock as a Potential Biomarker and Therapeutic Target in Gastrointestinal Cancers.Current pharmaceutical design · 2024Review
- Article
- The role of circadian clocks in cancer: Mechanisms and clinical implications.Genes & diseases · 2023Review
- CRS: a circadian rhythm score model for predicting prognosis and treatment response in cancer patients.Journal of translational medicine · 2023Article
- Review
- Myo1b promotes tumor progression and angiogenesis by inhibiting autophagic degradation of HIF-1α in colorectal cancer.Cell death & disease · 2022Article
- Loss of circadian gene Timeless induces EMT and tumor progression in colorectal cancer via Zeb1-dependent mechanism.Cell death and differentiation · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundColorectal cancer (CRC) is a common tumor characterized by its high mortality. However, the underlying molecular mechanisms that drive CRC tumorigenesis are unclear. Clock genes have important roles in tumor development. In the present study, the expression and functions of clock gene TIMELESS (encoding the Timeless protein) in CRC were investigated.
methodsImmunohistochemistry, cell proliferation, migration, invasion, EMT and xenograft tumor experiments were used to prove the function of Timeless in the tumorigenesis of CRC. Immunoprecipitation, mass spectrometry, Immunofluorescence and Chromatin immunoprecipitation (ChIP) were utilized to clarify the mechanism of Timeless in regulating CRC tumorigenesis.
resultsWe found that Timeless was upregulated in CRC tissues compared with corresponding normal tissues and its expression was closely associated with the TNM stages and overall survival of CRC patients. Functional studies demonstrated that Timeless promoted the proliferation, invasion, and EMT of CRC cells in vitro and in vivo. Mechanistic investigations showed that Timeless activated the β-catenin signal pathway by binding to Myosin-9, which binds to β-catenin to induce its nuclear translocation. The upregulation of Timeless was attributed to CREB-binding protein (CBP)/p300-mediated H3K27 acetylation of the promoter region of Timeless.
conclusionTimeless regulates the tumorigenesis of CRC by binding to and regulating myosin-9, suggesting Timeless might be a potential prognostic biomarker and therapeutic target for CRC.
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