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MEX3A knockdown inhibits the development of pancreatic ductal adenocarcinoma
Cancer Cell International ( IF 5.3 ) Pub Date : 2020-02-28 , DOI: 10.1186/s12935-020-1146-x
Xing Wang 1 , Yu-Qiang Shan 2 , Qing-Quan Tan 1 , Chun-Lu Tan 1 , Hao Zhang 1 , Jin-Heng Liu 1 , Neng-Wen Ke 1 , Yong-Hua Chen 1 , Xu-Bao Liu 1
Affiliation  

Pancreatic ductal adenocarcinoma (PDA) is one of the most serious causes of death in the world due to its high mortality and inefficacy treatments. MEX3A was first identified in nematodes and was associated with tumor formation and may promote cell proliferation and tumor metastasis. So far, nothing is known about the relationship between MEX3A and PDA. In this study, the expression level of MEX3A in PDA tissues was measured by immunohistochemistry. The qRT-PCR and western blot were used to identify the constructed MEX3A knockdown cell lines, which was further used to construct mouse xenotransplantation models. Cell proliferation, colony formation, cell apoptosis and migration were detected by MTT, colony formation, flow cytometry and Transwell. This study showed that MEX3A expression is significantly upregulated in PDA and associated with tumor grade. Loss-of-function studies showed that downregulation of MEX3A could inhibit cell growth in vitro and in vivo. Moreover, it was demonstrated that knockdown of MEX3A in PDA cells promotes apoptosis by regulating apoptosis-related factors, and inhibits migration through influencing EMT. At the same time, the regulation of PDA progression by MEX3A involves changes in downstream signaling pathways including Akt, p-Akt, PIK3CA, CDK6 and MAPK9. We proposed that MEX3A is associated with the prognosis and progression of PDA,which can be used as a potential therapeutic target.

中文翻译:

MEX3A 敲低抑制胰腺导管腺癌的发展

胰腺导管腺癌(PDA)由于其高死亡率和无效治疗而成为世界上最严重的死亡原因之一。MEX3A 首次在线虫中发现,与肿瘤形成有关,并可能促进细胞增殖和肿瘤转移。到目前为止,对于 MEX3A 和 PDA 之间的关系,我们一无所知。在这项研究中,通过免疫组织化学测量了 PDA 组织中 MEX3A 的表达水平。qRT-PCR和western blot用于鉴定构建的MEX3A敲低细胞系,进一步用于构建小鼠异种移植模型。通过MTT、集落形成、流式细胞仪和Transwell检测细胞增殖、集落形成、细胞凋亡和迁移。该研究表明,MEX3A 表达在 PDA 中显着上调,并与肿瘤分级相关。功能丧失研究表明,MEX3A 的下调可以在体外和体内抑制细胞生长。此外,研究表明 PDA 细胞中 MEX3A 的敲低通过调节凋亡相关因子促进细胞凋亡,并通过影响 EMT 抑制迁移。同时,MEX3A 对 PDA 进展的调节涉及下游信号通路的变化,包括 Akt、p-Akt、PIK3CA、CDK6 和 MAPK9。我们提出MEX3A与PDA的预后和进展有关,可作为潜在的治疗靶点。研究表明,PDA细胞中MEX3A的敲低通过调节细胞凋亡相关因子促进细胞凋亡,并通过影响EMT抑制迁移。同时,MEX3A 对 PDA 进展的调节涉及下游信号通路的变化,包括 Akt、p-Akt、PIK3CA、CDK6 和 MAPK9。我们提出MEX3A与PDA的预后和进展有关,可作为潜在的治疗靶点。研究表明,PDA细胞中MEX3A的敲低通过调节细胞凋亡相关因子促进细胞凋亡,并通过影响EMT抑制迁移。同时,MEX3A 对 PDA 进展的调节涉及下游信号通路的变化,包括 Akt、p-Akt、PIK3CA、CDK6 和 MAPK9。我们提出MEX3A与PDA的预后和进展有关,可作为潜在的治疗靶点。
更新日期:2020-02-28
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