2. Academic Validation
  3. PER3 promoter hypermethylation correlates to the progression of pan-cancer

PER3 promoter hypermethylation correlates to the progression of pan-cancer

  • Clin Epigenetics. 2024 Oct 14;16(1):140. doi: 10.1186/s13148-024-01760-5.
Yaoxu Li # 1 2,  Wenjuan Li # 3,  Jinhai Deng 2,  Mingzhu Yin 4 5 6
Affiliations

Affiliations

  • 1 Department of Stomatology, Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Wanzhou District, Chongqing, 404100, China.
  • 2 Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC) and Translational Medicine Research Center (TMRC), Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Wanzhou District, Chongqing, 404100, China.
  • 3 Department of Emergency and Critical Care Medicine, The First Afliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
  • 4 Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC) and Translational Medicine Research Center (TMRC), Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Wanzhou District, Chongqing, 404100, China. yinmingzhu2008@126.com.
  • 5 Chongqing Technical Innovation Center for Quality Evaluation and Identification of Authentic Medicinal Herbs, Wanzhou District, Chongqing, 404100, China. yinmingzhu2008@126.com.
  • 6 Three Gorges Hospital & Academy for Advanced Interdisciplinary Technology, CQU-Ferenc Krausz Nobel Laureate Scientific Workstation, Chongqing University, Chongqing, China. yinmingzhu2008@126.com.
  • # Contributed equally.
PMID: 39402618 DOI: 10.1186/s13148-024-01760-5
Abstract

Background: 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.

Results: 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.

Conclusions: Our findings advanced the mechanistic understanding of variations in PER3 expression in cancers and confirmed the tumor-associated function of PER3 hypermethylation and downregulation.

Keywords

Kidney renal papillary cell carcinoma; Lung adenocarcinoma; Methylation; Pan-cancer; Period circadian regulator 3; Promoter.

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