Qian Yun, Feng Limin, Wu Weigen, Weng Tianhao, Hu Chenyu, Hong Bo, Wang Frederick X C, Shen Lingwei, Wang Qi, Jin Xin, Yao Hangping
Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cell Physiol Biochem. 2017;44(2):494-504. doi: 10.1159/000485086. Epub 2017 Nov 17.
BACKGROUND/AIMS: Co-stimulating molecule B7-H4 regulates T cell-mediated immune responses, participates in tumor immune escape, and promotes the proliferation and metastasis of pancreatic cancer cells. However, the specific mechanisms are unclear. MicroRNAs (miRNAs) participated in the pathogenesis and progression of cancer.
In this study, a microarray technique was used to screen B7-H4-related differentially expressed miRNAs in a pancreatic cancer cell line find those associated with pancreatic cancer. Using a miRCURYTM LNA Array approach, we compared the miRNA expression profiles of L3.6p1 pancreatic cancer cells transfected with B7-H4 siRNA for 72 h with those transfected with non-target siRNAs.
B7-H4 siRNA significantly up-regulated 57 miRNAs and down-regulated 14 miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis of predicted miRNA targets showed that these genes were mainly involved in protein binding, pathways in cancer, mitogen-activated protein kinase (MAPK) signaling pathway, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway.
This is the first description of target genes of B7-H4, showing that miRNAs participate in the B7-H4 mediated regulation of oncogenicity and pathogenesis of pancreatic cancer. These results may help us better understand the role of B7-H4 in the progression of pancreatic cancer and its possible mechanisms. We also provide novel biomarkers for potential treatments of pancreatic cancer.
背景/目的：共刺激分子B7-H4调节T细胞介导的免疫反应，参与肿瘤免疫逃逸，并促进胰腺癌细胞的增殖和转移。然而，具体机制尚不清楚。微小RNA（miRNA）参与了癌症的发病机制和进展。
在本研究中，采用微阵列技术筛选胰腺癌细胞系中与B7-H4相关的差异表达miRNA，以发现与胰腺癌相关的miRNA。使用miRCURYTM LNA Array方法，我们比较了用B7-H4 siRNA转染72小时的L3.6p1胰腺癌细胞与用非靶向siRNA转染的细胞的miRNA表达谱。
B7-H4 siRNA显著上调了57种miRNA，下调了14种miRNA。对预测的miRNA靶标的基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析表明，这些基因主要参与蛋白质结合、癌症通路Mitogen-activated protein kinase（MAPK）信号通路和磷脂酰肌醇3-激酶-Akt（PI3K-Akt）信号通路。
这是首次对B7-H4的靶基因进行描述，表明miRNA参与了B7-H4介导的胰腺癌致癌性和发病机制的调节。这些结果可能有助于我们更好地理解B7-H4在胰腺癌进展中的作用及其可能的机制。我们还为胰腺癌的潜在治疗提供了新的生物标志物。
