1. KAT7 serves as an oncogenic gene and regulates CCL3 expression via STAT1 signaling in osteosarcoma.
- Author
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Yuan, Quan, Wu, Yuxuan, Xue, Cheng, Zhao, Deyong, Wang, Haibo, and Shen, Yixin
- Subjects
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GENE expression , *STAT proteins , *OSTEOSARCOMA , *HISTONE acetyltransferase , *TUMORS in children - Abstract
Osteosarcoma, considered as the primary cause of malignant bone tumors in children, necessitates novel therapeutic strategies to enhance overall survival rates. KAT7, a histone acetyltransferase, exerts pivotal functions in gene transcription and immune modulation. In light of this, our study identified a significant upregulation of KAT7 in the mRNA and protein levels in human osteosarcoma, boosting cell proliferation in vivo and in vitro. In addition, KAT7-mediated H3K14ac activation induced MMP14 transcription, leading to increased expression and facilitation of osteosarcoma cell metastasis. Subsequent bioinformatics analyses highlighted a correlation between KAT7 and adaptive immune responses, indicating CCL3 as a downstream target of KAT7. Mechanistically, STAT1 was found to transcriptionally upregulate CCL3 expression. Furthermore, overexpression of KAT7 suppressed CCL3 secretions, whereas knockdown of KAT7 enhanced its release. Overall, these findings underscore the oncogenic role of KAT7 in regulating immune responses for osteosarcoma treatment. • KAT7 was abundantly expressed in osteosarcoma. • KAT7 overexpression enhanced the expression of MMP14 by H3K14ac modification. • KAT7 inhibited the expression of CCL3 via JAK1-STAT1 signaling pathways. • STAT1 transcriptionally activated CCL3, thereby modulating immune responses. • KAT7 accelerated dissemination of OS cells in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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