Research progress of clock gene Period family in head and neck squamous cell carcinoma

doi:10.3760/cma.j.cn371439-20240927-00017

Abstract

Abstract:

Head and neck squamous cell carcinoma （HNSCC） is the most common type of heterogeneous malignant tumor. Over 60% of HNSCC patients are at locally advanced stage at the time of diagnosis. Despite the emergence of advanced diagnosis and treatment measures， the prognosis of patients with recurrent or metastatic HNSCC remains poor. The Period （PER） gene family is an important member of the circadian clock genes， with family members PER1， PER2， and PER3 showing differential expression in HNSCC， participating in biological processes such as proliferation， apoptosis， invasion， or metastasis of tumor cells. In most studies， they exhibit anti-cancer effects and are closely related to the tumor microenvironment， immunotherapy， chronotherapy， etc.， making them potential biomarkers. A comprehensive analysis of the expression of PER gene family in HNSCC， its biological role in the occurrence and development of tumor and the corresponding molecular biological mechanism is helpful to explore its potential application value in the diagnosis and treatment of HNSCC.

Key words: Squamous cell carcinoma of head and neck, Prognosis, Molecular targeted therapy, Tumor microenvironment, Period gene

Ye Yongying, Zou Yan, Chen Tianming, Wu Weili. Research progress of clock gene Period family in head and neck squamous cell carcinoma[J]. Journal of International Oncology, 2025, 52(2): 113-118.

References 43

[1]	Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024[J]. CA Cancer J Clin, 2024, 74(1): 12-49. DOI: 10.3322/caac.21820.
[2]	Mody MD, Rocco JW, Yom SS, et al. Head and neck cancer[J]. Lancet, 2021, 398(10318): 2289-2299. DOI: 10.1016/S0140-6736(21)01550-6.
[3]	Chen K, Wang Y, Li D, et al. Biological clock regulation by the PER gene family: a new perspective on tumor development[J]. Front Cell Dev Biol, 2024, 12: 1332506. DOI: 10.3389/fcell.2024.1332506.
[4]	Wang Q, Liu H, Wang Z, et al. Circadian gene Per3 promotes astroblastoma progression through the P53/BCL2/BAX signalling pathway[J]. Gene, 2024, 895: 147978. DOI: 10.1016/j.gene.2023.147978.
[5]	Rodríguez-Santana C, López-Rodríguez A, Martinez-Ruiz L, et al. The relationship between clock genes, sirtuin 1, and mitochondrial activity in head and neck squamous cell cancer: effects of melatonin treatment[J]. Int J Mol Sci, 2023, 24(19): 15030. DOI: 10.3390/ijms241915030.
[6]	He L, Ping F, Fan Z, et al. Salivary exosomal miR-24-3p serves as a potential detective biomarker for oral squamous cell carcinoma screening[J]. Biomed Pharmacother, 2020, 121: 109553. DOI: 10.1016/j.biopha.2019.109553. pmid: 31704611
[7]	Li YY, Jin F, Zhou JJ, et al. Downregulation of the circadian period family genes is positively correlated with poor head and neck squamous cell carcinoma prognosis[J]. Chronobiol Int, 2019, 36(12): 1723-1732. DOI: 10.1080/07420528.2019.1648486.
[8]	Aye L, Wang Z, Chen F, et al. Circadian regulator-mediated molecular subtypes depict the features of tumor microenvironment and indicate prognosis in head and neck squamous cell carcinoma[J]. J Immunol Res, 2023, 2023: 9946911. DOI: 10.1155/2023/9946911.
[9]	Gong X, Tang H, Yang K. PER1 suppresses glycolysis and cell proliferation in oral squamous cell carcinoma via the PER1/RACK1/PI3K signaling complex[J]. Cell Death Dis, 2021, 12(3): 276. DOI: 10.1038/s41419-021-03563-5. pmid: 33723221
[10]	Zhang J, Lv H, Ji M, et al. Low circadian clock genes expression in cancers: a meta-analysis of its association with clinicopathological features and prognosis[J]. PLoS One, 2020, 15(5): e0233508. DOI: 10.1371/journal.pone.0233508.
[11]	Zhang Z, Sun D, Tang H, et al. PER2 binding to HSP90 enhances immune response against oral squamous cell carcinoma by inhibiting IKK/NF-κB pathway and PD-L1 expression[J]. J Immunother Cancer, 2023, 11(11): e007627. DOI: 10.1136/jitc-2023-007627.
[12]	Yin S, Zhang Z, Tang H, et al. The biological clock gene PER1 affects the development of oral squamous cell carcinoma by altering the circadian rhythms of cell proliferation and apoptosis[J]. Chronobiol Int, 2022, 39(9): 1206-1219. DOI: 10.1080/07420528.2022.2082302.
[13]	Yang Y, Tang H, Zheng J, et al. The PER1/HIF-1alpha negative feedback loop promotes ferroptosis and inhibits tumor progression in oral squamous cell carcinoma[J]. Transl Oncol, 2022, 18: 101360. DOI: 10.1016/j.tranon.2022.101360.
[14]	Yang G, Yang Y, Tang H, et al. Loss of the clock gene Per1 promotes oral squamous cell carcinoma progression via the AKT/mTOR pathway[J]. Cancer Sci, 2020, 111(5): 1542-1554. DOI: 10.1111/cas.14362.
[15]	Zhang C, Dang D, Wang H, et al. Acircadian rhythm-related gene signature for predicting survival and drug response in HNSC[J]. Front Immunol, 2022, 13: 1029676. DOI: 10.3389/fimmu.2022.1029676.
[16]	Tampakakis E, Gangrade H, Glavaris S, et al. Heart neurons use clock genes to control myocyte proliferation[J]. Sci Adv, 2021, 7(49): eabh4181. DOI: 10.1126/sciadv.abh4181.
[17]	Gao Y, Wu Y, Zhang N, et al. IDH1 gene mutation activates Smad signaling molecules to regulate the expression levels of cell cycle and biological rhythm genes in human glioma U87-MG cells[J]. Mol Med Rep, 2021, 23(5): 354. DOI: 10.3892/mmr.2021.11993.
[18]	Pourali G, Ahmadzade AM, Arastonejad M, et al. The circadian clock as a potential biomarker and therapeutic target in pancreatic cancer[J]. Mol Cell Biochem, 2024, 479(5): 1243-1255. DOI: 10.1007/s11010-023-04790-4.
[19]	Hou L, Li H, Wang H, et al. The circadian clock gene PER2 enhances chemotherapeutic efficacy in nasopharyngeal carcinoma when combined with a targeted nanosystem[J]. J Mater Chem B, 2020, 8(24): 5336-5350. DOI: 10.1039/d0tb00595a. pmid: 32458942
[20]	Gil-Martín E, Ramos E, López-Muñoz F, et al. Potential of melatonin to reverse epigenetic aberrations in oral cancer: new findings[J]. EXCLI J, 2023, 22: 1280-1310. DOI: 10.17179/excli2023-6624. pmid: 38234969
[21]	Rahman S, Kraljević Pavelić S, Markova-Car E. Circadian (De) regulation in head and neck squamous cell carcinoma[J]. Int J Mol Sci, 2019, 20(11): 2662. DOI: 10.3390/ijms20112662.
[22]	Liu H, Gong X, Yang K. Overexpression of the clock gene Per2 suppresses oral squamous cell carcinoma progression by activating autophagy via the PI3K/AKT/mTOR pathway[J]. J Cancer, 2020, 11(12): 3655-3666. DOI: 10.7150/jca.42771. pmid: 32284762
[23]	Xiong H, Yang Y, Yang K, et al. Loss of the clock gene PER2 is associated with cancer development and altered expression of important tumor-related genes in oral cancer[J]. Int J Oncol, 2018, 52(1): 279-287. DOI: 10.3892/ijo.2017.4180. pmid: 29115399
[24]	Long W, Gong X, Yang Y, et al. Downregulation of PER2 promotes tumor progression by enhancing glycolysis via the phosphatidylinositol 3-kinase/protein kinase B pathway in oral squamous cell carcinoma[J]. J Oral Maxillofac Surg, 2020, 78(10): 1780. e1-1780.e14. DOI: 10.1016/j.joms.2020.05.035.
[25]	Li M, Sun D, Song N, et al. Mutant p53 in head and neck squamous cell carcinoma: molecular mechanism of gain-of-function and targeting therapy (review)[J]. Oncol Rep, 2023, 50(3): 162. DOI: 10.3892/or.2023.8599.
[26]	Cavga AD, Tardu M, Korkmaz T, et al. Cryptochrome deletion in p53 mutant mice enhances apoptotic and anti-tumorigenic responses to UV damage at the transcriptome level[J]. Funct Integr Genomics, 2019, 19(5): 729-742. DOI: 10.1007/s10142-019-00680-5.
[27]	Hou W, Hou W, Zhao X. Exploring transcriptomic databases: unraveling circadian gene disruptions in lower grade glioma[J]. Sci Rep, 2024, 14(1): 16960. DOI: 10.1038/s41598-024-67559-9. pmid: 39043735
[28]	Bieuville M, Dujon AM, Raven N, et al. When do tumours develop? Neoplastic processes across different timescales: age, season and round the circadian clock[J]. Evol Appl, 2024, 17(10): e70024. DOI: 10.1111/eva.70024.
[29]	Jin Y, Wang Z, Huang S, et al. Identify and validate circadian regulators as potential prognostic markers and immune infiltrates in head and neck squamous cell carcinoma[J]. Sci Rep, 2023, 13(1): 19939. DOI: 10.1038/s41598-023-46560-8.
[30]	Ao Y, Zhao Q, Yang K, et al. A role for the clock period circadian regulator 2 gene in regulating the clock gene network in human oral squamous cell carcinoma cells[J]. Oncol Lett, 2018, 15(4): 4185-4192. DOI: 10.3892/ol.2018.7825. pmid: 29541184
[31]	Carron J, Torricelli C, Silva JK, et al. microRNAs deregulation in head and neck squamous cell carcinoma[J]. Head Neck, 2021, 43(2): 645-667. DOI: 10.1002/hed.26533.
[32]	Zhao X, Zhu X, Cheng S, et al. MiR-29a/b/c regulate human circadian gene hPER1 expression by targeting its 3'UTR[J]. Acta Biochim Biophys Sin (Shanghai), 2014, 46(4): 313-317. DOI: 10.1093/abbs/gmu007.
[33]	Guo F, Tang Q, Chen G, et al. Aberrant expression and subcellular localization of PER2 promote the progression of oral squamous cell carcinoma[J]. Biomed Res Int, 2020, 2020: 8587458. DOI: 10.1155/2020/8587458.
[34]	Deng F, Yang K. Current status of research on the period family of clock genes in the occurrence and development of cancer[J]. J Cancer, 2019, 10(5): 1117-1123. DOI: 10.7150/jca.29212. pmid: 30854119
[35]	Shaashua L, Mayer S, Lior C, et al. Stromal expression of the core clock gene period 2 is essential for tumor initiation and metastatic colonization[J]. Front Cell Dev Biol, 2020, 8: 587697. DOI: 10.3389/fcell.2020.587697.
[36]	Chen M, Zhang L, Liu X, et al. PER1 is a prognostic biomarker and correlated with immune infiltrates in ovarian cancer[J]. Front Genet, 2021, 12: 697471. DOI: 10.3389/fgene.2021.697471.
[37]	Liu S, Cheng Y, Wang S, et al. Circadian clock genes modulate immune, cell cycle and apoptosis in the diagnosis and prognosis of pan-renal cell carcinoma[J]. Front Mol Biosci, 2021, 8: 747629. DOI: 10.3389/fmolb.2021.747629.
[38]	Lee Y, Field JM, Sehgal A. Circadian rhythms, disease and chronotherapy[J]. J Biol Rhythms, 2021, 36(6): 503-531. DOI: 10.1177/07487304211044301.
[39]	Santoni M, Molina-Cerrillo J, Santoni G, et al. Role of clock genes and circadian rhythm in renal cell carcinoma: recent evidence and therapeutic consequences[J]. Cancers (Basel), 2023, 15(2): 408. DOI: 10.3390/cancers15020408.
[40]	Zeng Y, Guo Z, Wu M, et al. Circadian rhythm regulates the function of immune cells and participates in the development of tumors[J]. Cell Death Discov, 2024, 10(1): 199. DOI: 10.1038/s41420-024-01960-1. pmid: 38678017
[41]	Tang Q, Xie M, Yu S, et al. Periodic oxaliplatin administration in synergy with PER2-mediated PCNA transcription repression promotes chronochemotherapeutic efficacy of OSCC[J]. Adv Sci (Weinh), 2019, 6(21): 1900667.
[42]	陈欣祎, 翁一鸣, 魏家燕, 等. 免疫检查点抑制剂在复发或转移性头颈部鳞状细胞癌治疗中的进展[J]. 国际肿瘤学杂志, 2023, 50(9): 553-557. DOI: 10.3760/cma.j.cn371439-20230410-00106.
[43]	Wu Y, Tao B, Zhang T, et al. Pan-cancer analysis reveals disrupted circadian clock associates with T cell exhaustion[J]. Front Immunol, 2019, 10: 2451. DOI: 10.3389/fimmu.2019.02451. pmid: 31708917