https://doi.org/10.4081/ejh.2023.3413
DPY30 promotes the growth and survival of osteosarcoma cell by regulating the PI3K/AKT signal pathway
Submitted: 27 March 2022
Accepted: 11 September 2022
Published: 22 December 2022
Accepted: 11 September 2022
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Osteosarcoma (OS) is characterized by aggressive features including invasiveness and high incidence of metastasis. OS patients with metastases are difficult to treat and suffer from a poor prognosis. DPY30 (protein dpy-30 homolog) is a key component of SET1/MLL family of H3K4 methyltransferases, which is implicated in the progression of multiple cancers. However, the potential functional engagement of DPY30 in OS remains to be unveiled. The objective of this study is to investigate the potential roles of DPY30 in the regulation of malignant phenotypes of OS cells. We examined DPY30 expression from a published dataset (GSE28424) as well as in OS tissues and adjacent normal tissues from OS patients. The association of DPY30 expression level and clinicopathologic parameters was assessed by Chi-square test. The role of DPY30 in regulating the malignant phenotype of OS cells and tumorigenesis was examined by in vitro functional assays and xenograft mouse model. We reported an upregulation of DPY30 in OS tumor tissues in both published dataset and clinical samples. A high level of DPY30 expression was associated with larger tumor size and more metastasis in OS patients, as well as poor overall survival. DPY30 knockdown in OS cells significantly impairs proliferation, migration and invasion, but induced cellular apoptosis. We further demonstrated that the agonist of PI3K/AKT pathway can rescue the inhibitory effects of DPY30 knockdown in OS cells. Together, our data indicate that DPY30 functions as an oncogene to promote the malignancy of OS cells possibly through PI3K/AKT pathway. The dependency of OS cells on DPY30 overexpression is a targetable vulnerability in OS cells.
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Ethics Approval
This study was approved by the Institute Research Ethics Committee of Yantaishan Hospital (no. 2018036), The animal use protocol has been reviewed and approved by the Animal Care and Use Ethical Committee of Yantaishan Hospital (no. 202106003)How to Cite
Cheng, G. ., An, F., Cao, Z., Zheng, M. ., Zhao, Z. ., & Wu, H. (2022). DPY30 promotes the growth and survival of osteosarcoma cell by regulating the PI3K/AKT signal pathway. European Journal of Histochemistry, 67(1). https://doi.org/10.4081/ejh.2023.3413
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