Key Laboratory of Ethnomedicine for Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China.
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Cancer Biomark. 2020;29(1):79-88. doi: 10.3233/CBM-191163.
Pancreatic cancer is a malignant tumor and its incidence has increased in recent years. Carboxypeptidase E (CPE) is a prohormone/proneuropeptide processing enzyme that has been shown to be associated with tumor growth and invasion in various cancers including pancreatic cancer.
To understand the molecular mechanism underlying the proliferative effects of CPE in cancer cells.
We down-regulated CPE gene expression in PANC-1 cell, a pancreatic cell line, and investigated mRNA, miRNA, circRNA and lncRNA expression profiling in PANC-1 cells from control group and CPE knock-down group by microarray analysis. We further validated the top 14 differentially expressed circRNAs by qRT-PCR.
Our results showed that CPE down-regulation caused decreased cell proliferation. The microarray data showed 107, 15, 299 and 360 differentially expressed mRNAs, miRNAs, circRNAs, and lncRNAs, respectively between control group and CPE knock-down group. Of Which, 41 mRNAs, 12 miRNAs, 133 circRNAs, and 262 lncRNAs were down-regulated; 66 mRNAs, 3 miRNAs, 166 circRNAs, and 98 lncRNAs were up-regulated. Bioinformatics analysis showed that the top significantly enriched pathways for the differentially expressed RNAs were related to cancer onset and/or progression, these included p53 signaling pathway, ECM-receptor interaction, focal adhesion and Wnt signaling pathway. We further performed network analysis to assess the mRNA, miRNA, circRNA and lncRNA correlations, and showed that HUWE1, hsa-miR-6780b-5p, has_circ_0058208 and lnc-G3BP1-3:8 were in the core position of the network.
Taken together, these results identified potential CPE regulated core genes and pathways for cell proliferation in pancreatic cancer cell, and therefore provide potential targets for the treatment of pancreatic cancer.
胰腺癌是一种恶性肿瘤，近年来其发病率有所增加。羧肽酶 E（CPE）是一种前激素/神经肽加工酶，已被证明与多种癌症（包括胰腺癌）的肿瘤生长和侵袭有关。
了解 CPE 在癌细胞增殖中的作用的分子机制。
我们在胰腺癌细胞系 PANC-1 中下调了 CPE 基因表达，并通过微阵列分析研究了对照组和 CPE 敲低组 PANC-1 细胞中的 mRNA、miRNA、circRNA 和 lncRNA 表达谱。我们进一步通过 qRT-PCR 验证了前 14 个差异表达的 circRNA。
我们的结果表明，CPE 下调导致细胞增殖减少。微阵列数据显示，对照组和 CPE 敲低组之间分别有 107、15、299 和 360 个差异表达的 mRNA、miRNA、circRNA 和 lncRNA。其中，41 个 mRNA、12 个 miRNA、133 个 circRNA 和 262 个 lncRNA 下调；66 个 mRNA、3 个 miRNA、166 个 circRNA 和 98 个 lncRNA 上调。生物信息学分析表明，差异表达 RNA 最显著富集的通路与癌症的发生和/或进展有关，包括 p53 信号通路、ECM-受体相互作用、焦点黏附和 Wnt 信号通路。我们进一步进行了网络分析，以评估 mRNA、miRNA、circRNA 和 lncRNA 的相关性，并显示 HUWE1、hsa-miR-6780b-5p、has_circ_0058208 和 lnc-G3BP1-3:8 位于网络的核心位置。
综上所述，这些结果确定了潜在的 CPE 调节胰腺癌细胞增殖的核心基因和通路，因此为胰腺癌的治疗提供了潜在的靶点。
