Dataset Information

CKB affects human osteosarcoma progression by regulating the p53 pathway.

ABSTRACT: This study aimed to explore the role of the creatine kinase B (CKB) gene in the development of human osteosarcoma (OS). Western blotting and qRT-PCR were performed to detect CKB expression in tissues and cells. CCK-8, colony formation, flow cytometry, Transwell, and cell scratch assays were performed to detect OS cell viability, proliferation, apoptosis, invasion, and migration. Gene set enrichment analysis (GSEA) was used to conduct signal pathway enrichment. CKB expression was higher in OS tissues and cells than that in normal tissues and cells. Silencing CKB expression reduced cell proliferation, migration, and invasion, and improved cell apoptosis in HOS cells, while overexpressing CKB increased cell proliferation, migration, and invasion, and decreased apoptosis in U2-OS cells. GSEA showed that CKB affected the p53 signaling pathway. Overexpression of CKB inhibited the protein expression of p53, p21, and Bax and promoted the expression of Bcl-2 and MDM2 in U2-OS cells. Conversely, silencing CKB promoted the protein expression of p53, p21, and Bax, and inhibited the expression of Bcl-2 and MDM2 in HOS cells. Silencing p53 could reverse the effect of the silencing CKB in HOS cells, and overexpressing p53 could reverse the effect of overexpressing CKB in U2-OS cells. Taken together, CKB affects the development of OS by regulating the activity of the p53 signaling pathway.

SUBMITTER: Zhou F

PROVIDER: S-EPMC9641398 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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CKB affects human osteosarcoma progression by regulating the p53 pathway.

Zhou Fengxin F Dou Xinli X Li Chenguang C

American journal of cancer research 20221015 10

This study aimed to explore the role of the creatine kinase B (CKB) gene in the development of human osteosarcoma (OS). Western blotting and qRT-PCR were performed to detect CKB expression in tissues and cells. CCK-8, colony formation, flow cytometry, Transwell, and cell scratch assays were performed to detect OS cell viability, proliferation, apoptosis, invasion, and migration. Gene set enrichment analysis (GSEA) was used to conduct signal pathway enrichment. CKB expression was higher in OS tis ...[more]

PMID: 36381321

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Project description:Background: Bromodomain-containing protein 7 (BRD7) is identified as a transcriptional regulator and plays an important role in the development and progression of various tumors. Our previous study demonstrated that BRD7 acts as a potential tumor suppressor in hepatocellular carcinoma (HCC). However, the specific molecular mechanism underlying the BRD7-mediated inhibition of HCC progression remains poorly understood. Methods: We performed ChIP-seq analysis to investigate the gene network mediated by BRD7. Immunohistochemical analysis was performed to analyze potential associations between the p53 and BRD7 expression and the effect of their overexpression on disease pathogenesis and outcome. In addition, we performed biological function experiments to determine the effect of BRD7 and p53 on these functions that are central to tumorigenesis. Finally, we employed a BALB/c model for execution of xenograft transplants to examine the effect of either overexpressing or under-expressing BRD7 and p53 on tumor growth in mice injected with cells. Results: Our results suggested that BRD7 regulates the p53 pathway. Specifically, BRD7 was demonstrated to upregulate the transcription level of p53 by directly binding to the upstream regulatory region of the p53 transcriptional initiation site, thereby enhancing its promoter activity. Moreover, immunohistochemical analysis showed that wild-type p53 (WTp53) expression is positively associated with BRD7 expression and survival of patients with HCC. Additionally,changes of p53 expression could affect the tumor suppressive role of BRD7 on HCC cell proliferation, migration/invasion, cell-cycle, and tumor growth in vitro and in vivo. Furthermore, changes of BRD7 expression in HCC cells significantly altered the expression of p53 signal-related molecules such as p21, Bax, Bcl2, and cyclin D1, indicating that BRD7 may positively regulate activation of the p53 pathway. Conclusions: Collectively, our results indicated that BRD7 exerts anti-tumor effects in HCC through transcriptionally activating p53 pathway. These critical roles of BRD7may provide some promising diagnostic and therapeutic targets for HCC.

Dataset Information

CKB affects human osteosarcoma progression by regulating the p53 pathway.

Publications

CKB affects human osteosarcoma progression by regulating the p53 pathway.

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