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

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 conta...

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Published in:International journal of molecular sciences 2023-09, Vol.24 (18), p.14301
Main Authors: Kim, Young-Gon, Park, Jisook, Park, Eun Young, Kim, Sang-Mi, Lee, Soo-Youn
Format: Article
Language:English
Subjects:
Biomarkers
Development and progression
Diabetes
Diabetes Mellitus - metabolism
Exosomes - genetics
Exosomes - metabolism
Genes
Glucose
Homeostasis
Humans
Hyperglycemia
Insulin Resistance
Islets of Langerhans - metabolism
Medical diagnosis
Medical prognosis
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Pancreatic beta cells
Pancreatic cancer
Pancreatic Neoplasms
Pancreatic Neoplasms - metabolism
Peptides
RNA polymerase
Type 2 diabetes
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241814301