Wang Wei, Wang Jie, Yang Chuanxin, Wang Jian
Department of Hepatobiliary and Pancreatic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
IUBMB Life. 2021 Jun;73(6):866-882. doi: 10.1002/iub.2468. Epub 2021 Apr 3.
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.
基因表达谱分析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，并聚焦于微小RNA（miR）-216a在胰腺癌（PC）中的功能。利用PC数据集GSE15471、GSE16515和GSE32676筛选PC中的差异表达基因（DEG）。一项miRNA微阵列分析和基因本体分析表明，miR-216a是PC中一种重要的差异表达miRNA。京都基因与基因组百科全书（KEGG）分析表明，miR-216a和DEG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靶向肾母细胞瘤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细胞的增殖和侵袭能力，而WT1的进一步上调则阻断了miR-216a的功能。KRT7的沉默减弱了WT1的致癌作用。体外实验结果在体内得到了验证。miR-216a高表达而WT1低表达表明PC患者预后较好。miR-216a/WT1/KRT7轴影响PI3K/AKT通路的活性。总之，本研究证明miR-216a抑制WT1表达并阻断KRT7转录，从而使PI3K/AKT信号失活并降低PC进展。
