DGKZ Acts as a Potential Oncogene in Osteosarcoma Proliferation Through Its Possible Interaction With ERK1/2 and MYC Pathway
DGKZ Acts as a Potential Oncogene in Osteosarcoma Proliferation Through Its Possible Interaction With ERK1/2 and MYC Pathway
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DGKZ 通过与 ERK1/2 和 MYC 通路的可能相互作用，成为骨肉瘤增殖中的潜在癌基因
DOI：
10.3389/fonc.2018.00655
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发表时间：
2019-01
影响因子：
4.7
通讯作者：
Shen Zan
中科院分区：
文献类型：
--
作者：
Yu Wenxi;Tang Lina;Lin Feng;Yao Yang;Shen Zan
骨肉瘤是儿童和青年人最常见的原发性骨肿瘤之一。大多数骨肉瘤患者的替代治疗选择有限，转移性患者的预后通常较差。因此，寻找新的有效的治疗靶点对骨肉瘤的治疗具有重要意义。甘油二酯激酶ζ（DGKZ）是最近发现的一个与某些人类肿瘤发生有关的基因。然而，DGKZ在骨肉瘤增殖中的作用尚不清楚。在这项研究中，DGKZ的表达首次在OS肿瘤样品中进行了研究，并与OS患者的不良预后相关。通过shRNA沉默DGKZ抑制骨肉瘤细胞生长并促进细胞凋亡。在体内，DGKZ的敲除还抑制异种移植肿瘤增殖，如通过生物发光成像和重量/体积测量所确定的。同时，AffymeGeneChip和Influencity Pathway Analysis（IPA）分析显示，DGKZ敲低导致MYC通路活性降低，并且MYC通路中的几个靶基因表达改变，包括CCND 1、CDKN 2B、CDK 6、PCNA和EGR 1。此外，免疫沉淀结合质谱（IP-MS）分析用于鉴定与OS细胞中DGKZ相互作用的蛋白质，并揭示ERK 1/2，一个关键的MYC相互作用因子，与DGKZ相关。总之，我们的研究表明，DGKZ可能通过与ERK 1/2和MYC通路的相互作用而在骨肉瘤中起癌基因的作用。
Osteosarcoma (OS) is one of the most common primary bone tumors in children and young adults. The majority of osteosarcoma patients have limited alternative therapeutic options and metastatic patients generally have a poor prognosis. Thus, it is important to explore novel effective therapeutic targets in the treatment of osteosarcoma. Diacylglycerol kinase zeta (DGKZ) is a recently identified gene potentially associated with certain human carcinogenesis. However, the role of DGKZ in proliferation of osteosarcoma is still unclear. In this study, DGKZ's expression was firstly investigated in OS tumor samples and correlated with poor outcome in OS patients. Silence of DGKZ by shRNA hampered osteosarcoma cell growth and promoted cell apoptosis in vitro. In vivo, DGKZ's knockout also suppressed xenograft tumor proliferation as determined by bioluminescence imaging and weight/volume measurements. Meanwhile, Affymetrix GeneChip and Ingenuity Pathway Analysis (IPA) revealed that DGKZ knockdown resulted in a decreased activity of MYC pathway, and several target genes expression in MYC pathway were altered, including CCND1, CDKN2B, CDK6, PCNA, and EGR1. Furthermore, immunoprecipitation coupled with mass spectrometry (IP-MS) analysis was used to identify proteins that interacted with DGKZ in OS cells and revealed ERK1/2, a key MYC-interactor, to associate with DGKZ. Together, our study demonstrated that DGKZ might act as an oncogene in osteosarcoma via its possible interaction with ERK1/2 and MYC pathway.
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影响因子：
3.8
作者：
Cai K;Mulatz K;Ard R;Nguyen T;Gee SH
通讯作者：
Gee SH
影响因子：
3.7
作者：
Ard R;Mulatz K;Pomoransky JL;Parks RJ;Trinkle-Mulcahy L;Bell JC;Gee SH
通讯作者：
Gee SH
DOI：
10.1200/jco.2002.20.3.776
发表时间：
2002-02
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
S. Bielack;B. Kempf‐Bielack;G. Delling;G. Exner;S. Flege;K. Helmke;R. Kotz;M. Salzer‐Kuntschik-M.-Salzer‐Kuntschi
通讯作者：
S. Bielack;B. Kempf‐Bielack;G. Delling;G. Exner;S. Flege;K. Helmke;R. Kotz;M. Salzer‐Kuntschik-M.-Salzer‐Kuntschi
影响因子：
3.3
作者：
Hirose, Masamichi;Takeishi, Yasuchika;Yamada, Mitsuhiko
通讯作者：
Yamada, Mitsuhiko
影响因子：
13.8
作者：
KANOH, H;YAMADA, K;SAKANE, F
通讯作者：
SAKANE, F