Pan-cancer analyses reveal genomics and clinical characteristics of the melatonergic regulators in cancer

Jian Zhang, Huali Jiang, Kunpeng Du, Tao Xie, Baiyao Wang, Chengcong Chen, Russel J. Reiter, Bohong Cen, Yawei Yuan

Research output: Contribution to journalArticlepeer-review

Abstract

Melatonin, an endogenous hormone, plays protective roles in cancer. In addition to regulating circadian rhythms, sleep, and neuroendocrine activity, melatonin functions in various survival pathways. However, the mechanisms of melatonin regulation in cancer remain unknown. In the present study, we performed a comprehensive characterization of melatonin regulators in 9125 tumor samples across 33 cancer types using multi-omic data from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia. In the genomic landscape, we identified the heterozygous amplification of AANAT and GPR50, and heterozygous deletion of PER3, CYP2C19, and MTNR1A as the dominant alteration events. Expression analysis revealed methylation-mediated downregulation of melatonergic regulator expression. In addition, we found that melatonergic regulator expression could be used to predict patient survival in various cancers. In depth, microRNA (miRNA) analysis revealed an miRNA-mRNA interaction network, and the deregulated miRNAs were involved in melatonin secretion and metabolism by targeting circadian clock genes. Pathway analysis showed that melatonergic regulators were associated with inhibition of apoptosis, the cell cycle, the DNA damage response, and activation of RAS/MAPK and RTK signaling pathways. Importantly, by mining the Genomics of Drug Sensitivity in Cancer database, we discovered a number of potential drugs that might target melatonergic regulators. In summary, this study revealed the genomic alteration and clinical characteristics of melatonergic regulators across 33 cancers, which might clarify the relationship between melatonin and tumorigenesis. Our findings also might provide a novel approach for the clinical treatment of cancers.

Original languageEnglish (US)
Article numbere12758
JournalJournal of pineal research
Volume71
Issue number3
DOIs
StatePublished - Oct 2021

Keywords

  • genomics
  • melatonin
  • methylation
  • neoplasms
  • prognosis

ASJC Scopus subject areas

  • Endocrinology

Fingerprint

Dive into the research topics of 'Pan-cancer analyses reveal genomics and clinical characteristics of the melatonergic regulators in cancer'. Together they form a unique fingerprint.

Cite this