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Hypermethylation of CCND2 in Lung and Breast Cancer Is a Potential Biomarker and Drug Target

1
Division of Breast Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 110, Taiwan
2
Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
3
Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
4
Ph.D Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan
5
Professional Master Program in Pharmaceutics and Biotechnology, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan
6
Institute of Fisheries Science, National Taiwan University, Taipei 110, Taiwan
7
Golden Biotechnology Corporation, 15F., No. 27-6, Sec. 2, Zhongzheng E. Rd, Taipei, TW 110, Taiwan
8
Graduate Institute of Pharmacognosy, Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, Taipei Medical University, Taipei 110, Taiwan
*
Author to whom correspondence should be addressed.
These authors are equal first author contributors to this work.
Int. J. Mol. Sci. 2018, 19(10), 3096; https://doi.org/10.3390/ijms19103096
Received: 6 August 2018 / Revised: 30 September 2018 / Accepted: 1 October 2018 / Published: 10 October 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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PDF [3162 KB, uploaded 10 October 2018]
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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. View Full-Text
Keywords: lung adenocarcinoma; triple-negative breast cancer (TNBC); hypermethylation; Antrodia camphorata; antroquinonol D; CCND2; tumor suppressor gene; prognostic factor; circulating cell-free DNA lung adenocarcinoma; triple-negative breast cancer (TNBC); hypermethylation; Antrodia camphorata; antroquinonol D; CCND2; tumor suppressor gene; prognostic factor; circulating cell-free DNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Hung, C.-S.; Wang, S.-C.; Yen, Y.-T.; Lee, T.-H.; Wen, W.-C.; Lin, R.-K. Hypermethylation of CCND2 in Lung and Breast Cancer Is a Potential Biomarker and Drug Target. Int. J. Mol. Sci. 2018, 19, 3096.

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