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Epigenetic suppression of the anti-aging gene KLOTHO in human prostate cancer cell lines

Animal Cells and Systems 2017년 21권 4호 p.223 ~ 232
서민규, 김민수, 장아라, 정현주, 노유헌, 김도희, 이재혁, 고기성, 명순철,
소속 상세정보
서민규 ( Seo Min-Kyu ) - Chung-Ang University College of Medicine Department of Urology
김민수 ( Kim Min-Su ) - Seoul Medical Center Department of Urology
장아라 ( Jang A-Ra ) - Chung-Ang University College of Medicine Department of Urology
정현주 ( Chung Hyun-Joo ) - Chung-Ang University College of Medicine Department of Urology
노유헌 ( Noh Yoo-Hun ) - Chung-Ang University College of Medicine Department of Anatomy and Cell Biology and Neurology
김도희 ( Kim Do-Hee ) - Naturesense Inc.
이재혁 ( Lee Jae-Hyouk ) - Chung-Ang University College of Medicine Department of Urology
고기성 ( Ko Ki-Sung ) - Chung-Ang University College of Medicine Department of Medicine
명순철 ( Myung Soon-Chul ) - Chung-Ang University College of Medicine Department of Urology

Abstract


KLOTHO was originally identified as an aging-suppressor gene that causes a human aging-like phenotype when tested in KLOTHO-deficient-mice. Recent evidence suggests that KLOTHO functions as a tumor suppressor by inhibiting Wnt signaling. KLOTHO gene silencing, including DNA methylation, has been observed in some human cancers. Aberrant activation of Wnt signaling plays a significant role in aging, and its silencing may be related to prostate cancer and other types of cancers. Thus, we investigated whether the expression of the anti-aging gene KLOTHO was associated with epigenetic changes in prostate cancer cell lines. KLOTHO mRNA was detected in the 22Rv1 cell line while it was not detected in DU145 and PC-3 cell lines. The restoration of KLOTHO mRNA in the DU145 and PC-3 cell lines was induced with a DNA methyltransferase inhibitor. Methylation-specific PCR was performed to determine the specific CpG sites in the KLOTHO promoter responsible for expression. In addition, the level of methylation was assessed in each CpG by performing bisulfite sequencing and quantitative pyrosequencing analysis. The results suggested a remarkable inverse relationship between KLOTHO expression and promoter methylation in prostate cancer cell lines.

키워드

Prostate cancer; aging; KLOTHO; epigenetic inactivation; DNA methylation

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