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Lookup NU author(s): Dr Wei-Yu Lin
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019, The Author(s). DNA methylation alteration, such as global hypomethylation and localized hypermethylation, within the promoters of tumor suppressor genes, is an important risk factor in cervical cancer. The potential use of DNA methylation detection, in cervical cancer screening or triage of mildly abnormal cytology, has recently been demonstrated. In particular, PAX1 DNA methylation testing was approved as an adjunct to cytology, in Taiwan, and is now undergoing registration trials in China. However, the function of PAX1 in cancer biology remains largely unknown. Here, we show that PAX1 inhibits malignant phenotypes upon oncogenic stress. Specifically, PAX1 expression inhibited the phosphorylation of multiple kinases, after challenges with oncogenic growth factors such as EGF and IL-6. Analogously, PAX1 activated a panel of phosphatases, including DUSP1, 5, and 6, and inhibited EGF/MAPK signaling. PAX1 also interacted with SET1B, increasing histone H3K4 methylation and DNA demethylation of numerous phosphatase-encoding genes. Furthermore, hypermethylated PAX1 associated with poor prognosis in cervical cancer. Taken together, this study reveals, for the first time, the functional relevance of PAX1 in cancer biology, and further supports the prospect of targeting multifold oncogenic kinase cascades, which jointly contribute to multiresistance, via epigenetic reactivation of PAX1.
Author(s): Su P-H, Lai H-C, Huang R-L, Chen L-Y, Wang Y-C, Wu T-I, Chan MWY, Liao C-C, Chen CW, Lin W-Y, Chang C-C
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2019
Volume: 9
Issue: 1
Online publication date: 24/06/2019
Acceptance date: 07/06/2019
Date deposited: 08/07/2019
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41598-019-45477-5
DOI: 10.1038/s41598-019-45477-5
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