PER3启动子高甲基化与Pan-Canter的进展相关
PER3 promoter hypermethylation correlates to the progression of pan-cancer
影响因子:4.40000
分区:医学2区 / 遗传学2区 肿瘤学2区
发表日期:2024 Oct 14
作者:
Yaoxu Li, Wenjuan Li, Jinhai Deng, Mingzhu Yin
摘要
恶性细胞表现出少量的昼夜节律调节剂3（PER3）表达。然而，癌症中PER3表达变化的潜在机制以及肿瘤进展中PER3的特定功能仍然很少理解。我们探索了多个公共数据库，进行了生物信息学分析，并在体外和体内实验进行了验证。我们发现，大多数类型的癌症中PER3表达降低，PER3下调与8种癌症的预后不良有关。在11种癌症中，PER3启动子甲基化水平升高。启动子过度甲基化（CPG岛[CGIS] CG12258811和CG14204433）与六种癌症（乳房浸润性癌，结肠腺癌，头部和颈部鳞状细胞癌，颈部鳞状癌，肾小球肾小球肾小球癌和KIRP]的PER3表达降低相关。子宫内膜癌）。 CGI CG12258811高甲基化与生存时间降低和晚期癌症阶段有关。此外，Bisulfite Pyrosequencing测定法证实了CGI CG12258811高甲基化及其与PER3表达的负相关性。体外和体内实验表明，PER 3抑制了KIRP和LUAD进展。 Decitabine通过减少启动子（CG12258811）甲基化水平抑制了PER3表达并抑制了KIRP细胞功能。您的发现提出了对CANCERS PER3表达变化的机械理解，并确认了PER3超甲基化和下调的肿瘤相关功能。
Abstract
Malignant cells exhibit reduced period circadian regulator 3 (PER3) expression. However, the underlying mechanisms of variations in PER3 expression in cancers and the specific function of PER3 in tumor progression remain poorly understood.We explored multiple public databases, conducted bioinformatics analyses, and performed in vitro and in vivo experiments for validation. We found PER3 expression was decreased in most types of cancers, and PER3 downregulation was associated with a poor prognosis in 8 types of cancer. PER3 promoter methylation levels were increased in 11 types of cancer. Promoter hypermethylation (CpG islands [CGIs] cg12258811 and cg14204433) correlated with decreased PER3 expression in six cancers (breast invasive carcinoma, colon adenocarcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma [KIRP], lung adenocarcinoma [LUAD], and uterine corpus endometrial carcinoma). CGI cg12258811 hypermethylation was associated with reduced survival time and advanced cancer stages. Moreover, the bisulfite pyrosequencing assay confirmed CGI cg12258811 hypermethylation and its negative correlation with PER3 expression. In vitro and in vivo experiments demonstrated that PER3 inhibited KIRP and LUAD progression. Decitabine enhanced PER3 expression and inhibited KIRP cell functions by reducing promoter (cg12258811) methylation level.Our findings advanced the mechanistic understanding of variations in PER3 expression in cancers and confirmed the tumor-associated function of PER3 hypermethylation and downregulation.