中国耳鼻咽喉头颈外科2025，Vol.32Issue(8)：512-517,6.DOI:10.16066/j.1672-7002.2025.08.008
周期昼夜节律调节器1通过NF-κB信号通路介导丝氨酸肽酶抑制因子Kazal 5型抑制头颈鳞状细胞癌增殖与迁移的机制研究
Mechanism of PER1-mediated inhibition of proliferation and migration in head and neck squamous cell carcinoma via the NF-κB signaling pathway by regulating SPINK5
摘要
Abstract
OBJECTIVE To investigate the expression characteristics and regulatory mechanisms of the circadian clock gene period circadian regulator 1(PER1)and the tumor suppressor gene serine peptidase inhibitor Kazal type 5(SPINK5)in head and neck squamous cell carcinoma(HNSCC),and to elucidate the molecular mechanism by which PER1 regulates SPINK5 transcription via the NF-κB signaling pathway.METHODS Differentially expressed genes in HNSCC were screened using The Cancer Genome Atlas(TCGA)and GSE205155 datasets.The association between SPINK5 expression and patient prognosis was assessed via the GEPIA database.mRNA and protein expression levels of SPINK5 and PER1 in 60 clinical samples were detected by RT-qPCR,immunohistochemistry,and Western blot.PER1 knockdown(using siRNA)and overexpression(via plasmid transfection)were performed in the AMC-HN-8 cell line.Wound healing and colony formation assays were applied to evaluate the effects of PER1,SPINK5,and their interaction on HNSCC cell migration and proliferation.Western blot was utilized to examine the regulatory effect of NF-κB on SPINK5.RESULTS SPINK5 and PER1 were significantly downregulated in HNSCC tissues(all P<0.01),and their low expression was correlated with poor patient prognosis(for SPINK5,HR=0.69,P=0.006 7).A significant positive correlation was observed between PER1 and SPINK5 expression(R²=0.719 2,P=0.001 0).Knockdown and overexpression of PER1 respectively resulted in synchronous alterations in SPINK5 mRNA levels(all P<0.05).PER1 knockdown enhanced cell migration and proliferation(P<0.05),whereas SPINK5 overexpression suppressed these capabilities(P<0.01).Importantly,SPINK5 overexpression reversed the phenotypic changes induced by PER1 knockdown.Mechanistically,PER1 overexpression led to concomitant changes in NF-κB expression,activating the NF-κB pathway and thereby promoting SPINK5 transcription.CONCLUSION PER1 positively regulates SPINK5 transcription via the NF-κB pathway,inhibiting HNSCC cell proliferation and migration.These findings suggest that PER1 and SPINK5 may serve as potential therapeutic targets for HNSCC.关键词
头颈鳞状细胞癌/细胞增殖/细胞迁移/周期昼夜节律调节器1/NF-κB信号通路Key words
Squamous Cell Carcinoma of Head and Neck/Cell Proliferation/Cell Migration Assays/period circadian regulator 1/NF-κB signaling pathway引用本文复制引用
刘婉琛,任超,宋西成,沈慧,牟亚魁,王浛睿,王瑶,杨婷,宋晓宇,张明君,程元潮..周期昼夜节律调节器1通过NF-κB信号通路介导丝氨酸肽酶抑制因子Kazal 5型抑制头颈鳞状细胞癌增殖与迁移的机制研究[J].中国耳鼻咽喉头颈外科,2025,32(8):512-517,6.基金项目
头颈肿瘤诊疗关键技术研发与应用推广(2022CXPT023) （2022CXPT023）
泰山学者(tstp20250521、tsqn202312392) （tstp20250521、tsqn202312392）
