Circadian clock as a possible control point in colorectal cancer progression (Review)

Int J Oncol. 2022 Dec;61(6):149. doi: 10.3892/ijo.2022.5439. Epub 2022 Oct 20.

Abstract

The circadian rhythm is generated at the cellular level by a molecular clock system that involves specific genes. Studies have revealed that circadian clock disruption is a control point in cancer progression. Colorectal cancer (CRC) is one of the cancers closely associated with circadian disruption. In the present review, the involvement of the circadian clock in CRC development was summarized. Abnormal expression of certain clock genes has been found in patients with CRC and their correlation with clinicopathological features has also been explored. The period and cryptochrome 2 (Cry2), Sirtuin1 (SIRT1) and neuronal PAS domain protein 2 (NPAS2) genes were reported to have tumour suppressor properties. Conversely, Cry1, brain and muscle ARNT‑like‑1, circadian locomotor output cycles kaput (CLOCK) and timeless may aggravate CRC progression, but these findings are not consistent and require to be confirmed by further research. Circadian scheduling also indicated advantages in chemotherapy treatments for patients with CRC by increasing the maximum tolerated doses and decreasing toxicities. Dysfunction of the molecular CLOCK system disrupted cellular processes to accelerate colon tumorigenesis, such as metabolism, cell cycle, DNA damage repair, proliferation and apoptosis, epithelial‑mesenchymal transition and stemness. The clock gene network and how the dynamics of the system influence CRC were discussed.

Keywords: BMAL1; CLOCK; TIM; circadian clock; colorectal cancer; cryptochrome; period.

Publication types

  • Review

MeSH terms

  • Cell Cycle
  • Circadian Clocks* / genetics
  • Circadian Rhythm / genetics
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Cryptochromes
  • Humans
  • Sirtuin 1

Substances

  • Cryptochromes
  • Sirtuin 1

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (grant no. 82104647), the Chinese Postdoctoral Science Foundation (grant no. 2021M700964) and Guangzhou Science and Technology Bureau (grant no. 201904010396).