Døssing Kristina B V, Kjær Christina, Vikeså Jonas, Binderup Tina, Knigge Ulrich, Culler Michael D, Kjær Andreas, Federspiel Birgitte, Friis-Hansen Lennart
Center for Genomic Medicine, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Genes (Basel). 2018 Jul 4;9(7):337. doi: 10.3390/genes9070337.
Somatostatin (SST) analogues are used to control the proliferation and symptoms of neuroendocrine tumors (NETs). MicroRNAs (miRNA) are small non-coding RNAs that modulate posttranscriptional gene expression. We wanted to characterize the miRNAs operating under the control of SST to elucidate to what extent they mediate STT actions. NCI-H727 carcinoid cell line was treated with either a chimeric SST/dopamine analogue; a SST or dopamine analogue for proliferation assays and for identifying differentially expressed miRNAs using miRNA microarray. The miRNAs induced by SST analogue treatment are investigated in carcinoid cell lines NCI-H727 and CNDT2 using in situ hybridization, qPCR and proliferation assays. SST analogues inhibited the growth of carcinoid cells more potently compared to the dopamine analogue. Principal Component Analysis (PCA) of the samples based on miRNA expression clearly separated the samples based on treatment. Two miRNAs which were highly induced by SST analogues, miR-7 and miR-148a, were shown to inhibit the proliferation of NCI-H727 and CNDT2 cells. SST analogues also produced a general up-regulation of the let-7 family members. SST analogues control and induce distinct miRNA expression patterns among which miR-7 and miR-148a both have growth inhibitory properties.
生长抑素（SST）类似物用于控制神经内分泌肿瘤（NETs）的增殖和症状。微小RNA（miRNA）是调节转录后基因表达的小非编码RNA。我们想要表征在SST控制下发挥作用的miRNA，以阐明它们在多大程度上介导SST的作用。用嵌合SST/多巴胺类似物、SST或多巴胺类似物处理NCI-H727类癌细胞系，用于增殖测定以及使用miRNA微阵列鉴定差异表达的miRNA。使用原位杂交、qPCR和增殖测定在类癌细胞系NCI-H727和CNDT2中研究SST类似物处理诱导的miRNA。与多巴胺类似物相比，SST类似物更有效地抑制类癌细胞的生长。基于miRNA表达对样本进行主成分分析（PCA），根据处理情况清晰地分离了样本。由SST类似物高度诱导的两种miRNA，miR-7和miR-148a，显示出抑制NCI-H727和CNDT2细胞增殖的作用。SST类似物还使let-7家族成员普遍上调。SST类似物控制并诱导不同的miRNA表达模式，其中miR-7和miR-148a均具有生长抑制特性。
