Pancreatic cancer (PC), a leading cause of cancer‐related deaths, has a 5‐year survival rate of approximately 10%. α‐Enolase (ENO1) is a junction channel protein involved in tumor cell apoptosis and chemoresistance. However, the role of ENO1 in PC remains unclear. The expression and prognosis of ENO1 levels were determined in PC using public databases based on The Cancer Genome Atlas (TCGA) data sets. Cell viability, half maximal inhibitory concentration (IC50), autophagy, apoptosis, and autophagy markers were examined using cell counting kit‐8 (CCK‐8), transmission electron microscope, flow cytometry assays, and immunoblot, respectively. Using the Gene Expression Omnibus (GEO) and TCGA data sets, we found that ENO1 was significantly enriched in PC tumor tissues, and high expression levels of ENO1 were associated with an unfavorable prognosis. Whereas ENO1 silencing suppressed proliferation, autophagy, and induced cell apoptosis in PC cells, and inhibited tumor growth in vivo. Mechanistically, knockdown of ENO1 enhanced cellular cytotoxicity of gemcitabine (GEM), as well as reducing the expression of yes‐associated protein 1 (YAP1), a major downstream effector of the Hippo pathway in vitro. YAP1 promoted autophagy and protected PC cells from GEM‐induced apoptotic cell death. Furthermore, YAP1 overexpression attenuated the inhibition effects of ENO1 silencing. Our results suggest that ENO1 overexpression promotes cell growth and tumor progression by increasing the expression of YAP1 in PC. Further studies are required to understand the detailed mechanisms between ENO1 and YAP1 in PC.

中文翻译：

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ENO1通过YAP1信号通路促进胰腺癌吉西他滨耐药

胰腺癌 (PC) 是癌症相关死亡的主要原因，其 5 年生存率约为 10%。 α-烯醇化酶（ENO1）是一种连接通道蛋白，参与肿瘤细胞凋亡和化疗耐药。然而，ENO1 在 PC 中的作用仍不清楚。 ENO1 水平的表达和预后是在 PC 中使用基于癌症基因组图谱 (TCGA) 数据集的公共数据库确定的。分别使用细胞计数试剂盒-8 (CCK-8)、透射电子显微镜、流式细胞术和免疫印迹检查细胞活力、半数抑制浓度 (IC50)、自噬、凋亡和自噬标记物。使用基因表达综合（GEO）和TCGA数据集，我们发现ENO1在PC肿瘤组织中显着富集，并且ENO1的高表达水平与不良预后相关。而ENO1沉默可抑制PC细胞的增殖、自噬并诱导细胞凋亡，并抑制体内肿瘤生长。从机制上讲，ENO1 的敲低增强了吉西他滨 (GEM) 的细胞毒性，并减少了 yes 相关蛋白 1 (YAP1) 的表达，yes 相关蛋白 1 (YAP1) 是体外 Hippo 途径的主要下游效应子。 YAP1 促进自噬并保护 PC 细胞免受 GEM 诱导的细胞凋亡。此外，YAP1 过表达减弱了 ENO1 沉默的抑制作用。我们的结果表明，ENO1 过表达通过增加 PC 中 YAP1 的表达来促进细胞生长和肿瘤进展。需要进一步的研究来了解 ENO1 和 YAP1 在 PC 中的详细机制。