Sun Guihua, Qi Meirigeng, Kim Alexis S, Lizhar Elizabeth M, Sun Olivia W, Al-Abdullah Ismail H, Riggs Arthur D
Department of Diabetes Complications & Metabolism, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA 91010, USA.
Department of Neurodegenerative Diseases, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Noncoding RNA. 2023 Mar 17;9(2):20. doi: 10.3390/ncrna9020020.
miRNAs are critical for pancreas development and function. However, we found that there are discrepancies regarding pancreatic miRNA abundance in published datasets. To obtain a more relevant profile that is closer to the true profile, we profiled small RNAs from human islets cells, acini, and four rodent pancreatic cell lines routinely used in diabetes and pancreatic research using a bias reduction protocol for small RNA sequencing. In contrast to the previous notion that miR-375-3p is the most abundant pancreatic miRNA, we found that miR-148a-3p and miR-7-5p were also abundant in islets. In silico studies using predicted and validated targets of these three miRNAs revealed that they may work cooperatively in endocrine and exocrine cells. Our results also suggest, compared to the most-studied miR-375, that both miR-148a-3p and miR-7-5p may play more critical roles in the human pancreas. Moreover, according to in silico-predicted targets, we found that miR-375-3p had a much broader target spectrum by targeting the coding sequence and the 5' untranslated region, rather than the conventional 3' untranslated region, suggesting additional unexplored roles of miR-375-3p beyond the pancreas. Our study provides a valuable new resource for studying miRNAs in pancreata.
微小RNA(miRNA)对胰腺的发育和功能至关重要。然而,我们发现在已发表的数据集中,胰腺miRNA丰度存在差异。为了获得更接近真实情况的相关图谱,我们使用一种针对小RNA测序的偏差减少方案,对来自人类胰岛细胞、腺泡以及糖尿病和胰腺研究中常用的四种啮齿动物胰腺细胞系的小RNA进行了分析。与之前认为miR - 375 - 3p是胰腺中最丰富的miRNA这一观点不同,我们发现miR - 148a - 3p和miR - 7 - 5p在胰岛中也很丰富。使用这三种miRNA的预测和验证靶点进行的计算机模拟研究表明,它们可能在内分泌和外分泌细胞中协同发挥作用。我们的结果还表明,与研究最多的miR - 375相比,miR - 148a - 3p和miR - 7 - 5p在人类胰腺中可能发挥更关键的作用。此外,根据计算机模拟预测的靶点,我们发现miR - 375 - 3p通过靶向编码序列和5'非翻译区,而非传统的3'非翻译区,具有更广泛的靶点谱,这表明miR - 375 - 3p在胰腺之外还有尚未被探索的作用。我们的研究为胰腺中miRNA的研究提供了宝贵的新资源。