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.

中文翻译：

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DPY30通过调控PI3K/AKT信号通路促进骨肉瘤细胞的生长和存活。

骨肉瘤 (OS) 具有侵袭性特征，包括侵袭性和高转移率。具有转移的 OS 患者难以治疗且预后不良。DPY30（蛋白质 dpy-30 同系物）是 H3K4 甲基转移酶 SET1/MLL 家族的关键组成部分，与多种癌症的进展有关。然而，DPY30 在 OS 中的潜在功能参与仍有待揭示。本研究的目的是研究 DPY30 在调节 OS 细胞恶性表型中的潜在作用。我们检查了已发表的数据集 (GSE28424) 中的 DPY30 表达以及来自 OS 患者的 OS 组织和邻近正常组织。DPY30 表达水平与临床病理参数的关联通过卡方检验进行评估。通过体外功能测定和异种移植小鼠模型检查 DPY30 在调节 OS 细胞的恶性表型和肿瘤发生中的作用。我们报告了已发表的数据集和临床样本中 OS 肿瘤组织中 DPY30 的上调。高水平的 DPY30 表达与 OS 患者更大的肿瘤大小和更多的转移以及较差的总体生存相关。OS 细胞中的 DPY30 敲低显着损害增殖、迁移和侵袭，但诱导细胞凋亡。我们进一步证明了 PI3K/AKT 通路的激动剂可以挽救 OS 细胞中 DPY30 敲低的抑制作用。总之，我们的数据表明 DPY30 作为致癌基因起作用，可能通过 PI3K/AKT 通路促进 OS 细胞的恶性肿瘤。