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miR-204 与人类胰岛中的内分泌表型有关,但不通过 MAFA 调节胰岛素 mRNA。

miR-204 is associated with an endocrine phenotype in human pancreatic islets but does not regulate the insulin mRNA through MAFA.

机构信息

Diabetes Research Institute, Division of Immunology, Transplantation and Infectious Disease, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Human Pathologies Genomic Diagnostics unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.

出版信息

Sci Rep. 2017 Oct 25;7(1):14051. doi: 10.1038/s41598-017-13622-7.

DOI:10.1038/s41598-017-13622-7
PMID:29070792
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5656581/
Abstract

miR-204 has been proposed to modulate insulin expression in human pancreatic islets by regulating the expression of the MAFA transcript, and in turn insulin transcription. We investigated miR-204 expression in pancreatic endocrine tumors (PET), a panel of human tissues, tissues derived from pancreatic islet purification, and in induced pluripotent stem cells (iPSCs) differentiated towards a pancreatic endocrine phenotype by quantitative real time RT-PCR or droplet digital PCR (ddPCR). In addition, we evaluated the effect of miR-204 up- or down-regulation in purified human islets and in the EndoC-βH1 cell line, as an experimental model of human pancreatic β cells. Our results confirm that miR-204 was enriched in insulin producing PET, in β cells within healthy pancreatic islets, and highly expressed in EndoC-βH1 cells. Moreover, in iPSCs miR-204 increased stepwise upon stimulated differentiation to insulin producing cells. However, up- or down-regulation of miR-204 in human islets and in EndoC-βH1 cells resulted in modest and not significant changes of the MAFA and INS mRNAs measured by ddPCR or c-peptide release. Our data confirm the association of miR-204 with a β cell endocrine phenotype in human pancreatic islets, but do not support its direct role in regulating the levels of insulin mRNA through MAFA.

摘要

miR-204 被提出通过调节 MAFA 转录物的表达,进而调节胰岛素转录,来调节人胰腺胰岛中的胰岛素表达。我们通过定量实时 RT-PCR 或液滴数字 PCR(ddPCR)在胰腺内分泌肿瘤(PET)、一组人类组织、从胰腺胰岛纯化中获得的组织以及分化为胰腺内分泌表型的诱导多能干细胞(iPSC)中研究了 miR-204 的表达。此外,我们评估了 miR-204 在纯化的人胰岛和 EndoC-βH1 细胞系中的上调或下调对实验模型人胰腺β细胞的影响。我们的结果证实 miR-204 在产生胰岛素的 PET 中丰富,在健康胰腺胰岛中的β细胞中丰富,并且在 EndoC-βH1 细胞中高度表达。此外,在 iPSC 中,miR-204 在刺激分化为产生胰岛素的细胞时逐步增加。然而,在人胰岛和 EndoC-βH1 细胞中上调或下调 miR-204 导致 ddPCR 或 C 肽释放测量的 MAFA 和 INS mRNA 的变化适度且无统计学意义。我们的数据证实了 miR-204 与人胰腺胰岛中β细胞内分泌表型的关联,但不支持其通过 MAFA 直接调节胰岛素 mRNA 水平的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/c4cb42d0e6d3/41598_2017_13622_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/747ee69b00d4/41598_2017_13622_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/e4bc6ace0fcf/41598_2017_13622_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/10ff789e9d38/41598_2017_13622_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/15e582b8ebe4/41598_2017_13622_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/9ea16ada2ab3/41598_2017_13622_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/0072aba62424/41598_2017_13622_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/c4cb42d0e6d3/41598_2017_13622_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/747ee69b00d4/41598_2017_13622_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/e4bc6ace0fcf/41598_2017_13622_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/365061169680/41598_2017_13622_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/10ff789e9d38/41598_2017_13622_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/15e582b8ebe4/41598_2017_13622_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/9ea16ada2ab3/41598_2017_13622_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/0072aba62424/41598_2017_13622_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2559/5656581/c4cb42d0e6d3/41598_2017_13622_Fig8_HTML.jpg

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