The Circadian Clock as a Potential Biomarker and Therapeutic Target in Gastrointestinal Cancers


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Abstract

:The circadian clock consists of a hierarchical multi-oscillator network of intracellular and intercellular mechanisms throughout the body that contributes to anticipating metabolic activity and maintaining system homeostasis in response to environmental cues and intrinsic stimuli. Over the past few years, genetic variations of core clock genes have been associated with cancer risk in several epidemiological studies. A growing number of epidemiological research studies have demonstrated a direct correlation between the disturbance of circadian rhythms and the growth of tumors, indicating that shift workers are more susceptible to malignancies of the colon, prostate, ovarian, breast, lung, and liver. One of the most related cancers with circadian rhythm is Gastrointestinal (GI) cancer, which is a leading cause of cancer-related mortality nowadays. The aim of this review was to demonstrate the effect of the clock gene network on the growth of GI cancer, providing molecular targets for GI cancer treatment, possible prognostic biomarkers, and guidance for treatment choices.

About the authors

Sama Barati

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Homina Saffar

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Shima Mehrabadi

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

Amir Avan

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

References

  1. Wang J, Huang Q, Hu X, et al. Disrupting circadian rhythm via the PER1-HK2 axis reverses trastuzumab resistance in gastric cancer. Cancer Res 2022; 82(8): 1503-17. doi: 10.1158/0008-5472.CAN-21-1820 PMID: 35255118
  2. Bechtold DA, Gibbs JE, Loudon ASI. Circadian dysfunction in disease. Trends Pharmacol Sci 2010; 31(5): 191-8. doi: 10.1016/j.tips.2010.01.002 PMID: 20171747
  3. Mehrabadi S, Izadi SF, Pasha S, et al. The potential therapeutic applications of CRISPR/Cas9 in the treatment of gastrointestinal cancers. Curr Mol Med 2024; 24 doi: 10.2174/0115665240243076231116080113 PMID: 38243923
  4. Kelleher FC, Rao A, Maguire A. Circadian molecular clocks and cancer. Cancer Lett 2014; 342(1): 9-18. doi: 10.1016/j.canlet.2013.09.040 PMID: 24099911
  5. Sahar S, Corsi SP. Metabolism and cancer: The circadian clock connection. Nat Rev Cancer 2009; 9(12): 886-96. doi: 10.1038/nrc2747 PMID: 19935677
  6. Battaglin F, Chan P, Pan Y, et al. Clocking cancer: The circadian clock as a target in cancer therapy. Oncogene 2021; 40(18): 3187-200. doi: 10.1038/s41388-021-01778-6 PMID: 33846572
  7. Kang Y, Mok S, Zong X, Cao Y. Abstract 3436: Circadian rhythm dysregulation with risk of gastrointestinal cancers: A large-scale prospective analysis. Cancer Res 2024; 84(S6): 3436-6. doi: 10.1158/1538-7445.AM2024-3436
  8. Avan A, Mehrabadi S, Velayati M, et al. Growth-hormone-releasing hormone as a prognostic biomarker and therapeutic target in gastrointestinal cancer. Curr Cancer Drug Targets 2023; 23(5): 346-53. doi: 10.2174/1568009623666221228094557 PMID: 36582060
  9. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70(1): 7-30. doi: 10.3322/caac.21590 PMID: 31912902
  10. Damavandi S, Avan A, Zafari N, et al. Remodeling of the gut microbiota in colorectal cancer and its association with obesity. Curr Pharm Des 2023; 29(4): 256-71. doi: 10.2174/1381612829666230118123018 PMID: 36654469
  11. Nagoshi E, Saini C, Bauer C, Laroche T, Naef F, Schibler U. Circadian gene expression in individual fibroblasts: Cell-autonomous and self-sustained oscillators pass time to daughter cells. Cell 2004; 119(5): 693-705. doi: 10.1016/j.cell.2004.11.015 PMID: 15550250
  12. Ohdo S. Chronotherapeutic strategy: Rhythm monitoring, manipulation and disruption. Adv Drug Deliv Rev 2010; 62(9-10): 859-75. doi: 10.1016/j.addr.2010.01.006 PMID: 20188774
  13. Froy O. Metabolism and circadian rhythms-implications for obesity. Endocr Rev 2010; 31(1): 1-24. doi: 10.1210/er.2009-0014 PMID: 19854863
  14. Mukherji A, Kobiita A, Ye T, Chambon P. Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs. Cell 2013; 153(4): 812-27. doi: 10.1016/j.cell.2013.04.020 PMID: 23663780
  15. Qandeel HG, Alonso F, Hernandez DJ, et al. Role of vagal innervation in diurnal rhythm of intestinal peptide transporter 1 (PEPT1). J Gastrointest Surg 2009; 13(11): 1976-85. doi: 10.1007/s11605-009-0984-6 PMID: 19707837
  16. Mollazadeh S, Mehrabadi S, Hassanian SM, et al. Photodynamic therapy as a desirable approach in the treatment of colorectal cancer, with special focus on photodynamic nanotherapeutics in immunotherapy. Curr Med Chem 2024; 31 doi: 10.2174/0109298673267788231208073338 PMID: 38275066
  17. Murgo E, Colangelo T, Bellet MM, Malatesta F, Mazzoccoli G. Role of the circadian gas-responsive hemeprotein NPAS2 in physiology and pathology. Biology 2023; 12(10): 1354. doi: 10.3390/biology12101354 PMID: 37887064
  18. Liang Y, Wang S, Huang X, Chai R, Tang Q, Yang R. Dysregulation of circadian clock genes as significant clinic factor in the tumorigenesis of hepatocellular carcinoma. Comput Math Methods Med. 2021; 2021: p. 8238833.
  19. Shangguan Z, Zhang Q. Period circadian regulator 3 (PER3) enhances sensitivity to radiotherapy in gastric cancer via Wnt/β- catenin pathway. Trop J Pharm Res 2023; 22: 1205-10.
  20. Qian L, Ding X, Fan X, et al. Identification and validation of a novel prognostic circadian rhythm-related gene signature for stomach adenocarcinoma. Chronobiol Int 2023; 40(6): 744-58. doi: 10.1080/07420528.2023.2205936 PMID: 37122167
  21. Zhang LL, He QK, Lv YN, Zhang ZJ, Xiang YK. Expression pattern and prognostic value of circadian clock genes in pancreatic adenocarcinoma. Chronobiol Int 2021; 38(5): 681-93. doi: 10.1080/07420528.2021.1890760 PMID: 33691542
  22. Hasakova K, Reis R, Vician M, Zeman M, Herichova I. Expression of miR-34a-5p is up-regulated in human colorectal cancer and correlates with survival and clock gene PER2 expression. PLoS One 2019; 14(10): e0224396. doi: 10.1371/journal.pone.0224396 PMID: 31658284
  23. Štorcelová M, Vicián M, Reis R, Zeman M, Herichová I. Expression of cell cycle regulatory factors hus1, gadd45a, rb1, cdkn2a and mre11a correlates with expression of clock gene per2 in human colorectal carcinoma tissue. Mol Biol Rep 2013; 40(11): 6351-61. doi: 10.1007/s11033-013-2749-2 PMID: 24062075
  24. Krugluger W, Brandstaetter A, Kállay E, et al. Regulation of genes of the circadian clock in human colon cancer: Reduced period-1 and dihydropyrimidine dehydrogenase transcription correlates in high-grade tumors. Cancer Res 2007; 67(16): 7917-22. doi: 10.1158/0008-5472.CAN-07-0133 PMID: 17699798
  25. Karantanos T, Theodoropoulos G, Gazouli M, et al. Expression of clock genes in patients with colorectal cancer. Int J Biol Markers 2013; 28(3): 280-5. doi: 10.5301/JBM.5000033 PMID: 23712462
  26. Alexander M, Burch JB, Steck S, et al. Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation. Oncol Rep 2015; 33(2): 935-41. doi: 10.3892/or.2014.3667 PMID: 25501848
  27. Holipah T, Hinoura T, Kozaka N, Kuroda Y. The correlation between PER3 rs2640908 polymorphism and colorectal Cancer in the Japanese population. Appl Cancer Res 2019; 39(1): 3. doi: 10.1186/s41241-019-0072-5
  28. Cao M, Wang Y, Xiao Y, et al. Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9. J Exp Clin Cancer Res 2021; 40(1): 162. doi: 10.1186/s13046-021-01936-4 PMID: 33971927
  29. Colangelo T, Carbone A, Mazzarelli F, et al. Loss of circadian gene Timeless induces EMT and tumor progression in colorectal cancer via Zeb1-dependent mechanism. Cell Death Differ 2022; 29(8): 1552-68. doi: 10.1038/s41418-022-00935-y PMID: 35034102
  30. Stokes K, Nunes M, Trombley C, Flôres DE, Wu G, Taleb Z. The circadian clock gene, bmal1, regulates intestinal stem cell signaling and represses tumor initiation. Cell Mol Gastroenterol Hepatol 2021; 12(5): 1847-1872.e0. doi: 10.1016/j.jcmgh.2021.08.001
  31. Sahar N, Qadir J, Riaz SK, Sultan A, Arif A, Malik MFA. Dysregulation of core circadian genes, BMAL1 and CLOCK, in colorectal cancer. Biol Rhythm Res 2022; 53(9): 1400-13. doi: 10.1080/09291016.2021.1940623
  32. Cheng LT, Tan GYT, Chang FP, et al. Core clock gene BMAL1 and RNA-binding protein MEX3A collaboratively regulate Lgr5 expression in intestinal crypt cells. Sci Rep 2023; 13(1): 17597. doi: 10.1038/s41598-023-44997-5 PMID: 37845346
  33. Huisman SA, Ahmadi AR, IJzermans JNM, Verhoef C, van der Horst GTJ, de Bruin RWF. Disruption of clock gene expression in human colorectal liver metastases. Tumour Biol 2016; 37(10): 13973-81. doi: 10.1007/s13277-016-5231-7 PMID: 27492458
  34. Hasakova K, Vician M, Reis R, Zeman M, Herichova I. The expression of clock genes cry1 and cry2 in human colorectal cancer and tumor adjacent tissues correlates differently dependent on tumor location. Neoplasma 2018; 65(6): 986-92. doi: 10.4149/neo_2018_180122N47 PMID: 29940771
  35. He Y, Chen Y, Dai X, Huang S. Dysregulation of circadian clock genes associated with tumor immunity and prognosis in patients with colon cancer. Comput Math Methods Med 2022; 2022: 4957996.
  36. He A, Huang Z, Zhang R, et al. Circadian clock genes are correlated with prognosis and immune cell infiltration in colon adenocarcinoma. Comput Math Methods Med 2022; 2022: 1709918. doi: 10.1155/2022/4957996 PMID: 35116071
  37. Hu ML, Yeh KT, Lin PM, et al. Deregulated expression of circadian clock genes in gastric cancer. BMC Gastroenterol 2014; 14(1): 67. doi: 10.1186/1471-230X-14-67 PMID: 24708606
  38. Karantanos T, Theodoropoulos G, Pektasides D, Gazouli M. Clock genes: Their role in colorectal cancer. World J Gastroenterol 2014; 20(8): 1986-92. doi: 10.3748/wjg.v20.i8.1986 PMID: 24587674
  39. Papantoniou K, Vinyals CG, Espinosa A, et al. Sleep duration and napping in relation to colorectal and gastric cancer in the MCC-Spain study. Sci Rep 2021; 11(1): 11822. doi: 10.1038/s41598-021-91275-3 PMID: 34083698
  40. Zhao H, Zeng Z-L, Yang J, et al. Prognostic relevance of Period1 (Per1) and Period2 (Per2) expression in human gastric cancer. Int J Clin Exp Pathol 2014; 7(2): 619-30. PMID: 24551282
  41. Tian Y, Xie Y, Bai F, Zhang D. Identification of circadian determinants of cancer chronotherapy through in vitro chronopharmacology and mathematical modeling. Molecul Cancer Therap 2022; 14: 2154-64. doi: 10.21203/rs.3.rs-2142367/v1
  42. Zheng Z X, Cai X, Bi J T, Liu Y Q. The expression and prognostic significance of circadian gene NR1D1/2 in patients with gastric cancer. Res Sq 2023. doi: 10.21203/rs.3.rs-2560341/v1
  43. Cao X, Kang W, Xia T, Yuan S, Guo C, Wang W. High expression of the circadian clock gene NPAS2 is associated with progression and poor prognosis of gastric cancer: A single-center study. World J Gastroenterol 2023; 29(23): 3645-57. doi: 10.21203/rs.3.rs-2483331/v1
  44. He Q, Guo P, Lin Y, Zhang Z, Lv Y, Xiang Y. Genomics and prognosis analysis of circadian clock genes in hepatocellular carcinoma. Res Sq 2020. doi: 10.21203/rs.3.rs-35099/v1
  45. Lin YM, Chang JH, Yeh KT, Yang MY, Liu TC, Lin SF. Disturbance of circadian gene expression in hepatocellular carcinoma. Mol Carcinog 2008; 47(12): 925-33. doi: 10.1002/mc.20446
  46. Zhu M, Zhang J, Bian S, et al. Circadian gene CSNK1D promoted the progression of hepatocellular carcinoma by activating Wnt/β- catenin pathway via stabilizing dishevelled segment polarity protein 3. Biol Proced Online 2022; 24(1): 21. doi: 10.1186/s12575-022-00183-x PMID: 36460966
  47. Tavano F, Pazienza V, Fontana A, et al. SIRT1 and circadian gene expression in pancreatic ductal adenocarcinoma: Effect of starvation. Chronobiol Int 2015; 32(4): 497-512. doi: 10.3109/07420528.2014.1003351 PMID: 25798752
  48. Wong VCL, Ko JMY, Qi RZ, et al. Abrogated expression of DEC1 during oesophageal squamous cell carcinoma progression is age- and family history-related and significantly associated with lymph node metastasis. Br J Cancer 2011; 104(5): 841-9. doi: 10.1038/bjc.2011.25 PMID: 21326238
  49. Cheng J, Chen F, Cheng Y. Construction and evaluation of a risk score model for lymph node metastasis-associated circadian clock genes in esophageal squamous carcinoma. Cells 2022; 11(21): 3432. doi: 10.3390/cells11213432 PMID: 36359828
  50. Fuhr L, El-Athman R, Scrima R, et al. The circadian clock regulates metabolic phenotype rewiring via HKDC1 and modulates tumor progression and drug response in colorectal cancer. EBioMedicine 2018; 33: 105-21. doi: 10.1016/j.ebiom.2018.07.002 PMID: 30005951
  51. Brandi G, Calabrese C, Pantaleo MA, et al. Circadian variations of rectal cell proliferation in patients affected by advanced colorectal cancer. Cancer Lett 2004; 208(2): 193-6. doi: 10.1016/j.canlet.2003.11.015 PMID: 15142678
  52. Dulong S, Huang Q, Innominato PF, et al. Circadian and chemotherapy-related changes in urinary modified nucleosides excretion in patients with metastatic colorectal cancer. Sci Rep 2021; 11(1): 24015. doi: 10.1038/s41598-021-03247-2 PMID: 34907230
  53. Parascandolo A, Bonavita R, Astaburuaga R, et al. Effect of naive and cancer-educated fibroblasts on colon cancer cell circadian growth rhythm. Cell Death Dis 2020; 11(4): 289. doi: 10.1038/s41419-020-2468-2 PMID: 32341349
  54. Abolmaali K, Balakrishnan A, Stearns AT, et al. Circadian variation in intestinal dihydropyrimidine dehydrogenase (DPD) expression: A potential mechanism for benefits of 5FU chrono-chemotherapy. Surgery 2009; 146(2): 269-73. doi: 10.1016/j.surg.2009.05.005 PMID: 19628084
  55. Lévi F, Focan C, Karaboué A, et al. Implications of circadian clocks for the rhythmic delivery of cancer therapeutics. Adv Drug Deliv Rev 2007; 59(9-10): 1015-35. doi: 10.1016/j.addr.2006.11.001 PMID: 17692427
  56. BH JG, Shankar SJ, Munisamy M, RS A, Sagar VS. Development of pH-dependent chronomodulated delivery systems of 5-fluorouracil and oxaliplatin to treat colon cancer. Int J App Pharm 2020; 12: 118-30.
  57. Dulong S, Ballesta A, Okyar A, Lévi F. Identification of circadian determinants of cancer chronotherapy through in vitro chronopharmacology and mathematical modeling. Mol Cancer Ther 2015; 14(9): 2154-64. doi: 10.1158/1535-7163.MCT-15-0129 PMID: 26141947
  58. Innominato PF, Ballesta A, Huang Q, et al. Sex-dependent least toxic timing of irinotecan combined with chronomodulated chemotherapy for metastatic colorectal cancer: Randomized multicenter EORTC 05011 trial. Cancer Med 2020; 9(12): 4148-59. doi: 10.1002/cam4.3056 PMID: 32319740
  59. Hesse J, Martinelli J, Aboumanify O, Ballesta A, Relógio A. A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer. Comput Struct Biotechnol J 2021; 19: 5170-83. doi: 10.1016/j.csbj.2021.08.051 PMID: 34630937
  60. Basti A, Malhan D, Dumbani M, Dahlmann M, Stein U, Relógio A. Core-clock genes regulate proliferation and invasion via a reciprocal interplay with MACC1 in colorectal cancer cells. Cancers 2022; 14(14): 3458. doi: 10.3390/cancers14143458 PMID: 35884519
  61. Wei W, Zhao W, Zhang Y. CBX4 provides an alternate mode of colon cancer development via potential influences on circadian rhythm and immune infiltration. Front Cell Dev Biol 2021; 9: 669254. doi: 10.3389/fcell.2021.669254 PMID: 34222240
  62. Yu F, Zhang T, Zhou C, et al. The circadian clock gene Bmal1 controls intestinal exporter MRP2 and drug disposition. Theranostics 2019; 9(10): 2754-67. doi: 10.7150/thno.33395 PMID: 31244920
  63. Fuhr L, Basti A, Brás TS, Duarte MF, Relógio A. Antiproliferative effects of cynara cardunculus in colorectal cancer cells are modulated by the circadian clock. Int J Mol Sci 2022; 23(16): 9130. doi: 10.3390/ijms23169130 PMID: 36012399
  64. Moreno-SanJuan S, Puentes-Pardo JD, Casado J, et al. Agomelatine, a melatonin-derived drug, as a new strategy for the treatment of colorectal cancer. Antioxidants 2023; 12(4): 926. doi: 10.3390/antiox12040926 PMID: 37107301
  65. Lévi F, Karaboué A, Gorden L, et al. Cetuximab and circadian chronomodulated chemotherapy as salvage treatment for metastatic colorectal cancer (mCRC): Safety, efficacy and improved secondary surgical resectability. Cancer Chemother Pharmacol 2011; 67(2): 339-48. doi: 10.1007/s00280-010-1327-8 PMID: 20401611
  66. Okazaki F, Matsunaga N, Hamamura K, et al. Administering xCT inhibitors based on circadian clock improves antitumor effects. Cancer Res 2017; 77(23): 6603-13. doi: 10.1158/0008-5472.CAN-17-0720 PMID: 29038345
  67. Zeng Z, Luo H, Yang J, et al. Overexpression of the circadian clock gene Bmal1 increases sensitivity to oxaliplatin in colorectal cancer. Clin Cancer Res 2014; 20(4): 1042-52. doi: 10.1158/1078-0432.CCR-13-0171 PMID: 24277452
  68. Fang L, Yang Z, Zhou J, et al. Circadian clock gene CRY2 degradation is involved in chemoresistance of colorectal cancer. Mol Cancer Ther 2015; 14(6): 1476-87. doi: 10.1158/1535-7163.MCT-15-0030 PMID: 25855785
  69. Li XM, Djafari MA, Dumitru M, et al. A circadian clock transcription model for the personalization of cancer chronotherapy. Cancer Res 2013; 73(24): 7176-88. doi: 10.1158/0008-5472.CAN-13-1528 PMID: 24154875

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