基因敲除
体内
癌变
免疫组织化学
癌症研究
污渍
恶性肿瘤
下调和上调
细胞生长
癌症
生物
细胞凋亡
免疫学
基因
遗传学
作者
Tianming Zhao,Hanlong Zhu,Tianhui Zou,Si Zhao,Lin Zhou,Muhan Ni,Feng Liu,Hao Zhu,Xiaotan Dou,Jian Di,Bing Xu,Lei Wang,Xiaoping Zou
出处
期刊:Oncogenesis
[Springer Nature]
日期:2024-02-05
卷期号:13 (1)
被引量:3
标识
DOI:10.1038/s41389-024-00509-2
摘要
Abstract Pancreatic ductal adenocarcinoma (PDAC) is recognized as the most aggressive and fatal malignancy. A previous study reported that PDAC patients who exhibit elevated levels of DDX3X have a poor prognosis and low overall survival rate. However, the underlying molecular mechanism remains unclear. This study aimed to investigate the specific roles of DDX3X in PDAC. Multiple bioinformatics analyses were used to evaluate DDX3X expression and its potential role in PDAC. In vitro and in vivo studies were performed to assess the effects of DDX3X on PDAC cell growth. Furthermore, Western blotting, quantitative PCR, immunohistochemistry, immunofluorescence, mass spectrometry, coimmunoprecipitation and multiplexed immunohistochemical staining were conducted to identify the specific regulatory mechanism in PDAC. The results verified that DDX3X expression is notably upregulated in the tumor tissue vs. normal tissue of PDAC patients. DDX3X knockdown markedly suppressed the proliferation, invasion and migration of PDAC cells in vitro and inhibited tumor growth in vivo. Conversely, overexpression of DDX3X induced the opposite effect. Further studies supported that the DDX3X protein can associate with sirtuin 7 (SIRT7) to stimulate PDAC carcinogenesis and progression. Furthermore, SIRT7 inhibition significantly impeded DDX3X-mediated tumor growth both ex vivo and in vivo. The results also revealed that programmed death ligand 1 (PD-L1) expression is positively correlated with DDX3X expression. These results reveal significant involvement of the DDX3X-SIRT7 axis in the initiation and advancement of PDAC and offer previously undiscovered therapeutic options for PDAC management.
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