Jiang Xiuli, Shan Aijing, Su Yutong, Cheng Yulong, Gu Weiqiong, Wang Weiqing, Ning Guang, Cao Yanan
Shanghai Clinical Center for Endocrine and Metabolic Diseases (X.J., A.S., Y.S., Y.C., W.G., W.W., G.N., Y.C.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China.
Endocrinology. 2015 Jul;156(7):2429-39. doi: 10.1210/en.2014-1966. Epub 2015 Apr 28.
Insulinoma is the main type of functional pancreatic neuroendocrine tumors. The functional microRNAs (miRNAs) regulating tumor growth and progression in insulinomas are still unknown. We conducted the miRNA expression profile analysis using miRNA quantitative RT-PCR array and identified 114 differentially expressed miRNAs in human insulinomas compared with normal pancreatic islets. Forty-one differentially expressed miRNAs belonged to 7 miRNA families, and 28 miRNAs in 3 of the families localized in the epigenetically regulated imprinted chromosome 14q32 region. We validated the most significant differentially expressed miRNA cluster miR-144/451 in another 8 human normal islet samples and 25 insulinomas. Our data showed that the overexpression of miR-144/451 in mouse pancreatic β-cells promoted cell proliferation by targeting the β-cell regulator phosphatase and tensin homolog deleted on chromosome ten/v-akt murine thymoma viral oncogene homolog pathway and cyclin-dependent kinase inhibitor 2D. Our findings highlight the importance of functional miRNAs in insulinomas.
胰岛素瘤是功能性胰腺神经内分泌肿瘤的主要类型。调节胰岛素瘤肿瘤生长和进展的功能性微小RNA（miRNA）仍然未知。我们使用miRNA定量RT-PCR阵列进行了miRNA表达谱分析，并鉴定出与正常胰岛相比，人类胰岛素瘤中有114种差异表达的miRNA。41种差异表达的miRNA属于7个miRNA家族，其中3个家族中的28种miRNA定位于表观遗传调控的印记染色体14q32区域。我们在另外8个人类正常胰岛样本和25个胰岛素瘤中验证了差异表达最显著的miRNA簇miR-144/451。我们的数据表明，miR-144/451在小鼠胰腺β细胞中的过表达通过靶向β细胞调节因子10号染色体缺失的磷酸酶和张力蛋白同源物/v-akt小鼠胸腺瘤病毒癌基因同源物途径以及细胞周期蛋白依赖性激酶抑制剂2D促进细胞增殖。我们的研究结果突出了功能性miRNA在胰岛素瘤中的重要性。
