KAT6A is associated with sorafenib resistance and contributes to progression of hepatocellular carcinoma by targeting YAP
Autor: | Ding Jingyi, Jinzhen Cai, Fengqi Zhu, Cunle Zhu, Jin Yan, Qingguo Xu, Ruonan Yang |
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Rok vydání: | 2021 |
Předmět: |
Sorafenib
Carcinoma Hepatocellular Cell Survival Cell Biophysics Antineoplastic Agents Cell Cycle Proteins urologic and male genital diseases Biochemistry Epigenesis Genetic Histone H3 Cell Line Tumor medicine Gene silencing Humans heterocyclic compounds Epigenetics Viability assay neoplasms Molecular Biology Histone Acetyltransferases Cell growth business.industry Reverse Transcriptase Polymerase Chain Reaction Liver Neoplasms Cell Biology Hep G2 Cells medicine.disease female genital diseases and pregnancy complications digestive system diseases Gene Expression Regulation Neoplastic medicine.anatomical_structure Drug Resistance Neoplasm Hepatocellular carcinoma Cancer research Disease Progression business medicine.drug Transcription Factors |
Zdroj: | Biochemical and biophysical research communications. 585 |
ISSN: | 1090-2104 |
Popis: | Hepatocellular carcinoma (HCC) is a prevalent solid cancer worldwide and sorafenib is a common treatment. Nevertheless, sorafenib resistance is a severe clinical problem. In the present study, we identified that epigenetic regulator, KAT6A, was overexpressed in clinical HCC tissues and sorafenib-resistant HCC samples. The depletion of KAT6A repressed the cell viability and Edu-positive cell numbers of HCC cells. The IC50 value of sorafenib was increased in sorafenib-resistant HCC cells. In addition, the expression of KAT6A was induced in sorafenib-resistant HCC cells. The depletion of KAT6A suppressed the IC50 of sorafenib. Mechanically, YAP was decreased by the depletion of KAT6A. KAT6A was able to enrich in the promoter of YAP. The silencing of KAT6A reduced the enrichment of histone H3 lysine 23 acetylation (H3K23ac) and RNA polymerase II (RNA pol II) on the promoter of YAP in sorafenib-resistant HCC cells. KAT6A inhibitor WM-1119 repressed the cell proliferation of sorafenib-resistant HCC cells, while overexpression of KAT6A or YAP could reverse the effect in the cells. Meanwhile, the treatment of sorafenib inhibited the viability of sorafenib-resistant HCC cells, while the co-treatment of WM-1119 could improve the effect of sorafenib. Collectively, KAT6A was associated with sorafenib resistance and contributes to progression of HCC by targeting YAP. Targeting KAT6A may be served as a promising therapeutic approach for HCC. |
Databáze: | OpenAIRE |
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