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分析胰腺癌衍生外泌体处理后的胰岛细胞中差异表达的 microRNA 特征。

Analysis of MicroRNA Signature Differentially Expressed in Pancreatic Islet Cells Treated with Pancreatic Cancer-Derived Exosomes.

机构信息

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Sep 19;24(18):14301. doi: 10.3390/ijms241814301.

DOI:10.3390/ijms241814301
PMID:37762604
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10532014/
Abstract

Since the majority of patients with pancreatic cancer (PC) develop insulin resistance and/or diabetes mellitus (DM) prior to PC diagnosis, PC-induced diabetes mellitus (PC-DM) has been a focus for a potential platform for PC detection. In previous studies, the PC-derived exosomes were shown to contain the mediators of PC-DM. In the present study, the response of normal pancreatic islet cells to the PC-derived exosomes was investigated to determine the potential biomarkers for PC-DM, and consequently, for PC. Specifically, changes in microRNA (miRNA) expression were evaluated. The miRNA specimens were prepared from the untreated islet cells as well as the islet cells treated with the PC-derived exosomes (from 50 patients) and the healthy-derived exosomes (from 50 individuals). The specimens were subjected to next-generation sequencing and bioinformatic analysis to determine the differentially expressed miRNAs (DEmiRNAs) only in the specimens treated with the PC-derived exosomes. Consequently, 24 candidate miRNA markers, including IRS1-modulating miRNAs such as hsa-miR-144-5p, hsa-miR-3148, and hsa-miR-3133, were proposed. The proposed miRNAs showed relevance to DM and/or insulin resistance in a literature review and pathway analysis, indicating a potential association with PC-DM. Due to the novel approach used in this study, additional evidence from future studies could corroborate the value of the miRNA markers discovered.

摘要

由于大多数胰腺癌 (PC) 患者在 PC 诊断前就已经出现胰岛素抵抗和/或糖尿病 (DM)，因此 PC 诱导的糖尿病 (PC-DM) 一直是 PC 检测的潜在平台焦点。在之前的研究中，已经表明 PC 来源的外泌体包含 PC-DM 的介质。在本研究中，研究了正常胰岛细胞对 PC 来源的外泌体的反应，以确定用于 PC-DM 继而用于 PC 的潜在生物标志物。具体而言，评估了微小 RNA (miRNA) 表达的变化。从未处理的胰岛细胞以及用 PC 来源的外泌体（来自 50 名患者）和健康来源的外泌体（来自 50 个人）处理的胰岛细胞制备 miRNA 标本。对标本进行下一代测序和生物信息学分析，以确定仅在用 PC 来源的外泌体处理的标本中差异表达的 miRNA (DEmiRNA)。因此，提出了包括 IRS1 调节 miRNA 在内的 24 个候选 miRNA 标志物，如 hsa-miR-144-5p、hsa-miR-3148 和 hsa-miR-3133。通过文献回顾和途径分析，提出的 miRNA 与 DM 和/或胰岛素抵抗相关，表明其与 PC-DM 有潜在关联。由于本研究采用了新方法，未来研究的更多证据可能证实所发现的 miRNA 标志物的价值。

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