期刊
INTERNATIONAL JOURNAL OF CANCER
卷 131, 期 3, 页码 E179-E189出版社
WILEY-BLACKWELL
DOI: 10.1002/ijc.26501
关键词
human carcinogenesis; epigenetics; KDM3A; HOXA1
类别
资金
- Japan Society for the Promotion of Science [22681030]
- NIHR
- Cambridge Biomedical Research Centre
- Cancer Research UK [19275] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [22681030, 22134008, 21390178] Funding Source: KAKEN
A number of histone demethylases have been identified and biochemically characterized, yet their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. In this study, we describe important roles for the histone demethylase KDM3A, also known as JMJD1A, in human carcinogensis. Expression levels of KDM3A were significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues (p < 0.0001), when assessed by real-time PCR. We confirmed that some other cancers including lung cancer also overexpressed KDM3A, using cDNA microarray analysis. Treatment of cancer cell lines with small interfering RNA targeting KDM3A significantly knocked down its expression and resulted in the suppression of proliferation. Importantly, we found that KDM3A activates transcription of the HOXA1 gene through demethylating histone H3 at lysine 9 di-methylation by binding to its promoter region. Indeed, expression levels of KDM3A and HOXA1 in several types of cancer cell lines and bladder cancer samples were statistically correlated. We observed the down-regulation of HOXA1 as well as CCND1 after treatment with KDM3A siRNA, indicating G1 arrest of cancer cells. Together, our results suggest that elevated expression of KDM3A plays a critical role in the growth of cancer cells, and further studies may reveal a cancer therapeutic potential in KDM3A inhibition.
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