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Journal Publication
Title of Article High glucose-ROS conditions enhance the progression in cholangiocarcinoma via upregulation of MAN2A2 and CHD8 
Date of Acceptance 27 October 2020 
Journal
     Title of Journal Cancer Science 
     Standard ISI 
     Institute of Journal Cancer Science 
     ISBN/ISSN DOI: 10.1111/cas.14719 
     Volume 2020 
     Issue 112 
     Month October
     Year of Publication 2021 
     Page 254-264 
     Abstract Diabetes is a major risk factor in the development and progression of several cancers including cholangiocarcinoma (CCA). However, the molecular mechanism by which hyperglycemia potentiates progression of CCA is not clearly understood. Here, we showed that a high glucose condition significantly increased reactive oxygen species (ROS) production and promoted aggressive phenotypes of CCA cells, including pro- liferation and migration activities. Mannosidase alpha class 2a member 2 (MAN2A2), was upregulated at both mRNA and protein levels in a high glucose- and ROS- dependent manner. In addition, cell proliferation and migration were significantly reduced by MAN2A2 knockdown. Based on our proteome and in silico analyses, we further found that chromodomain helicase DNA-binding protein 8 (CHD8) was in- duced by ROS signaling and regulated MAN2A2 expression. Overexpression of CHD8 increased MAN2A2 expression, while CHD8 knockdown dramatically reduced prolif- eration and migration as well as MAN2A2 expression in CCA cells. Moreover, both MAN2A2 and CHD8 were highly expressed with positive correlation in CCA tumor tissues. Collectively, these data suggested that high glucose conditions promote CCA progression through ROS-mediated upregulation of MAN2A2 and CHD8. Thus, glu- cose metabolism is a promising therapeutic target to control tumor progression in patients with CCA and diabetes. 
     Keyword CHD8, cholangiocarcinoma, high glucose, MAN2A2, reactive oxygen species 
Author
597070040-9 Miss UNCHALEE THONSRI [Main Author]
Medicine Doctoral Degree

Reviewing Status มีผู้ประเมินอิสระ 
Status ตีพิมพ์แล้ว 
Level of Publication นานาชาติ 
citation false 
Part of thesis true 
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