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Review

Evaluation of the Circadian Rhythm Component Cipc (Clock-Interacting Pacemaker) in Leukemogenesis: A Literature Review and Bioinformatics Approach

by
Leidivan Sousa da Cunha
1,†,
Beatriz Maria Dias Nogueira
1,†,
Flávia Melo Cunha de Pinho Pessoa
1,
Caio Bezerra Machado
1,
Deivide de Sousa Oliveira
1,
Manoel Odorico de Moraes Filho
1,
Maria Elisabete Amaral de Moraes
1,
André Salim Khayat
2 and
Caroline Aquino Moreira-Nunes
1,2,3,4,*
1
Department of Medicine, Clinical Genetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil
2
Department of Biological Sciences, Oncology Research Center, Federal University of Pará, Belém 66077-830, PA, Brazil
3
Brazilian Institute of Intelligence in Health, Research and Education, IBISPE, Fortaleza 60160-230, CE, Brazil
4
Clementino Fraga Group, Central Unity, Molecular Biology Laboratory, Fortaleza 60455-970, CE, Brazil
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Clocks & Sleep 2025, 7(3), 33; https://doi.org/10.3390/clockssleep7030033
Submission received: 14 February 2025 / Revised: 12 June 2025 / Accepted: 24 June 2025 / Published: 25 June 2025
(This article belongs to the Section Human Basic Research & Neuroimaging)
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Abstract

Circadian rhythms (CRs) are a key biological system regulating physiological processes such as metabolism, cell growth, DNA repair, and immunity, adapting to environmental changes like the light/dark cycle. Governed by internal clocks, it modulates gene expression through feedback loops involving Clock Genes (CGs), with the cycle initiated by CLOCK–BMAL1 and NPAS2–BMAL1 heterodimers. Disruptions in circadian rhythms have been linked to diseases including metabolic disorders, neurodegeneration, and cancer. CIPC (CLOCK-interacting pacemaker) has been studied as a negative regulator of the CLOCK–BMAL1 complex, focusing on its role in cancer, particularly leukemias. Public datasets and bioinformatics tools were used to examine CIPC gene expression in healthy patients and acute myeloid leukemia (AML) samples. Our analysis revealed significant overexpression of CIPC in AML compared to healthy tissues (p < 0.0001 ****). Additionally, survival analysis indicated significant differences in overall survival based on CIPC expression, with a log-rank test p-value = 0.014, suggesting that CIPC expression may affect overall patient survival. Altered CIPC expression may contribute to leukemogenesis by inhibiting circadian genes, which are often disrupted in leukemia. Furthermore, CIPC interacts with oncogenic pathways, including the MAPK/ERK pathway, which is essential for cell proliferation. Additional studies are needed to validate these findings and explore the detailed role of CIPC in cancer development.
Keywords: circadian rhythms; leukemia; gene expression circadian rhythms; leukemia; gene expression

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MDPI and ACS Style

da Cunha, L.S.; Nogueira, B.M.D.; de Pinho Pessoa, F.M.C.; Machado, C.B.; de Sousa Oliveira, D.; de Moraes Filho, M.O.; de Moraes, M.E.A.; Khayat, A.S.; Moreira-Nunes, C.A. Evaluation of the Circadian Rhythm Component Cipc (Clock-Interacting Pacemaker) in Leukemogenesis: A Literature Review and Bioinformatics Approach. Clocks & Sleep 2025, 7, 33. https://doi.org/10.3390/clockssleep7030033

AMA Style

da Cunha LS, Nogueira BMD, de Pinho Pessoa FMC, Machado CB, de Sousa Oliveira D, de Moraes Filho MO, de Moraes MEA, Khayat AS, Moreira-Nunes CA. Evaluation of the Circadian Rhythm Component Cipc (Clock-Interacting Pacemaker) in Leukemogenesis: A Literature Review and Bioinformatics Approach. Clocks & Sleep. 2025; 7(3):33. https://doi.org/10.3390/clockssleep7030033

Chicago/Turabian Style

da Cunha, Leidivan Sousa, Beatriz Maria Dias Nogueira, Flávia Melo Cunha de Pinho Pessoa, Caio Bezerra Machado, Deivide de Sousa Oliveira, Manoel Odorico de Moraes Filho, Maria Elisabete Amaral de Moraes, André Salim Khayat, and Caroline Aquino Moreira-Nunes. 2025. "Evaluation of the Circadian Rhythm Component Cipc (Clock-Interacting Pacemaker) in Leukemogenesis: A Literature Review and Bioinformatics Approach" Clocks & Sleep 7, no. 3: 33. https://doi.org/10.3390/clockssleep7030033

APA Style

da Cunha, L. S., Nogueira, B. M. D., de Pinho Pessoa, F. M. C., Machado, C. B., de Sousa Oliveira, D., de Moraes Filho, M. O., de Moraes, M. E. A., Khayat, A. S., & Moreira-Nunes, C. A. (2025). Evaluation of the Circadian Rhythm Component Cipc (Clock-Interacting Pacemaker) in Leukemogenesis: A Literature Review and Bioinformatics Approach. Clocks & Sleep, 7(3), 33. https://doi.org/10.3390/clockssleep7030033

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