Abstract：
Early metastasis of pancreatic cancer (PaC) is a major cause of its high mortality rate. Previous studies have shown that AHNAK2 is involved in the progression of some tumors and is predicted to be an independent prognostic factor for PaC; however, the specific mechanisms through which AHNAK2 regulates PaC remain unclear. In this study, we examined the role of AHNAK2 in PaC and its potential molecular mechanisms. AHNAK2 mRNA and protein expression in PaC tissues and cells were measured using qRT-PCR and western blot analysis. After AHNAK2 knockdown using small interfering RNA, PaC cells were subjected to CCK-8 scratch, and Transwell assays to assess cell proliferation, migration, and invasion, respectively. Furthermore, the validation of the mechanistic pathway was achieved by western blot analysis. AHNAK2 mRNA and protein levels were up-regulated in PaC and silencing AHNAK2 significantly inhibited the proliferation, migration, and invasion of PaC cells. Mechanistically, AHNAK2 knockdown decreased the expression of phosphorylated p65, phosphorylated IκBα, and matrix metalloproteinase-9 (MMP-9), suggesting that activation of the NF-κB/MMP-9 signaling pathway was inhibited. Importantly, activation of NF-κB reversed the effects of AHNAK2 knockdown. Our findings indicate that AHNAK2 promotes PaC progression through the NF-kB/MMP-9 pathway and provides a theoretical basis for targeting AHNAK2 for the treatment of PaC.
摘要：
胰腺癌(PaC)的早期转移是其高死亡率的主要原因。先前的研究表明，AHNAK2参与了一些肿瘤的进展，并被预测为PaC的独立预后因素；然而，AHNAK2调控PaC的具体机制尚不清楚.在这项研究中,我们研究了AHNAK2在PaC中的作用及其潜在的分子机制。使用qRT-PCR和蛋白质印迹分析测量PaC组织和细胞中的AHNAK2mRNA和蛋白质表达。AHNAK2敲低后使用小干扰RNA，对PaC细胞进行CCK-8划痕,和Transwell分析来评估细胞增殖，迁移,和入侵,分别。此外，通过westernblot分析对机制途径进行了验证.AHNAK2mRNA和蛋白水平在PaC中上调，沉默AHNAK2显著抑制其增殖，迁移,以及PaC细胞的侵袭。机械上,AHNAK2敲除降低磷酸化p65、磷酸化IκBα的表达,和基质金属蛋白酶-9（MMP-9），提示NF-κB/MMP-9信号通路的激活受到抑制。重要的是,NF-κB的激活逆转了AHNAK2敲低的作用。我们的发现表明AHNAK2通过NF-kB/MMP-9通路促进PaC的进展，为靶向AHNAK2治疗PaC提供了理论依据。
