Gene expression profiling has been broadly performed in the field of cancer research. This study aims to explore the key gene regulatory network and focuses on the functions of microRNA (miR)-216a in pancreatic cancer (PC). PC datasets GSE15471, GSE16515, and GSE32676 were used to screen the differentially expressed genes (DEGs) in PC. A miRNA microarray analysis and gene oncology analysis suggested miR-216a as an important differentially expressed miRNA in PC. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that miR-216a and the DEGs are largely enriched on the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. miR-216a targeted Wilms Tumor 1 (WT1), while WT1 promoted transcription activity of keratin 7 (KRT7). Upregulation of miR-216a reduced proliferation and invasiveness of PC cells, while further upregulation of WT1 blocked the functions of miR-216a. Silencing of KRT7 diminished the oncogenic role of WT1. The in vitro results were reproduced in vivo. High expression of miR-216a while poor expression of WT1 indicated better prognosis of PC patients. The miR-216a/WT1/KRT7 axis influenced the activity of the PI3K/AKT pathway. To conclude, this study evidenced that miR-216a suppressed WT1 expression and blocked KRT7 transcription, which inactivated the PI3K/AKT signaling and reduced PC progression.

中文翻译：

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MicroRNA-216a 靶向 WT1 表达并调节 KRT7 转录以介导胰腺癌的进展——转录组分析

基因表达谱已在癌症研究领域广泛开展。本研究旨在探索关键基因调控网络，重点关注 microRNA (miR)-216a 在胰腺癌 (PC) 中的功能。PC 数据集 GSE15471、GSE16515 和 GSE32676 用于筛选 PC 中的差异表达基因 (DEG)。miRNA 微阵列分析和基因肿瘤学分析表明 miR-216a 是 PC 中重要的差异表达 miRNA。京都基因和基因组百科全书 (KEGG) 分析表明 miR-216a 和 DEGs 在很大程度上富集于磷脂酰肌醇 3-激酶/蛋白激酶 B (PI3K/AKT) 信号通路。miR-216a 靶向 Wilms Tumor 1 (WT1)，而 WT1 促进角蛋白 7 (KRT7) 的转录活性。miR-216a 的上调降低了 PC 细胞的增殖和侵袭性，而WT1的进一步上调阻断了miR-216a的功能。KRT7 的沉默降低了 WT1 的致癌作用。体外结果在体内重现。miR-216a的高表达而WT1的低表达表明PC患者的预后较好。miR-216a/WT1/KRT7 轴影响 PI3K/AKT 通路的活性。总之，这项研究证明 miR-216a 抑制 WT1 表达并阻断 KRT7 转录，从而使 PI3K/AKT 信号失活并减少 PC 进展。