Hypermethylation of CCND2 in Lung and Breast Cancer Is a Potential Biomarker and Drug Target
Journal
International Journal of Molecular Sciences
Journal Volume
19
Journal Issue
10
Pages
pii: E3096
Date Issued
2018
Author(s)
Abstract
Lung and breast cancer are the leading causes of mortality in women worldwide. The discovery of molecular alterations that underlie these two cancers and corresponding drugs has contributed to precision medicine. We found that CCND2 is a common target in lung and breast cancer. Hypermethylation of the CCND2 gene was reported previously; however, no comprehensive study has investigated the clinical significance of CCND2 alterations and its applications and drug discovery. Genome-wide methylation and quantitative methylation-specific real-time polymerase chain reaction (PCR) showed CCND2 promoter hypermethylation in Taiwanese breast cancer patients. As compared with paired normal tissues and healthy individuals, CCND2 promoter hypermethylation was detected in 40.9% of breast tumors and 44.4% of plasma circulating cell-free DNA of patients. The western cohort of The Cancer Genome Atlas also demonstrated CCND2 promoter hypermethylation in female lung cancer, lung adenocarcinoma, and breast cancer patients and that CCND2 promoter hypermethylation is an independent poor prognostic factor. The cell model assay indicated that CCND2 expression inhibited cancer cell growth and migration ability. The demethylating agent antroquinonol D upregulated CCND2 expression, caused cell cycle arrest, and inhibited cancer cell growth and migration ability. In conclusion, hypermethylation of CCND2 is a potential diagnostic, prognostic marker and drug target, and it is induced by antroquinonol D. ? 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Antrodia camphorata; Antroquinonol D; CCND2; Circulating cell-free DNA; Hypermethylation; Lung adenocarcinoma; Prognostic factor; Triple-negative breast cancer (TNBC); Tumor suppressor gene
SDGs
Other Subjects
antroquinonol; antroquinonol D; biological marker; CCND2 antigen; cell antigen; genomic DNA; sulforhodamine B; unclassified drug; antineoplastic agent; antroquinonol; CCND2 protein, human; cyclin D2; messenger RNA; tumor marker; ubiquinone; Antrodia camphorata; Article; breast cancer; breast tissue; cancer staging; cancer tissue; CCND2 gene; cell cycle arrest; cell migration; cell migration assay; cell proliferation; CL1-5 cell line; colon cancer; controlled study; DNA methylation; drug isolation; drug targeting; enzyme activity; esophagus cancer; female; gene; gene expression; human; human cell; human tissue; IC50; liver cancer; lung cancer; major clinical study; metastasis; mRNA expression level; NCI-H1299 cell line; overall survival; polymerase chain reaction; promoter region; protein expression; pyrosequencing; real time polymerase chain reaction; rectum cancer; RNA extraction; RNA sequence; stomach cancer; triple negative breast cancer; tumor growth; tumor suppressor gene; Western blotting; wound healing assay; analogs and derivatives; antagonists and inhibitors; breast tumor; cell motion; dose response; drug effect; gene expression regulation; genetics; lung tumor; mortality; prognosis; proportional hazards model; Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Cell Movement; Cell Proliferation; Cyclin D2; DNA Methylation; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Prognosis; Promoter Regions, Genetic; Proportional Hazards Models; RNA, Messenger; Ubiquinone
Publisher
MDPI
Type
journal article