Heterogeneity study on miRNAs expression in islet cells of rat pancreatic head and tail
Background:As a vital endocrine organ, the pancreas, which has differences in terms of anatomical structure and microenvironment between the pancreatic head and tail. However, it is currently unclear whether there is heterogeneity in miRNAs expression within the islet cells of these two regions and what biological significance this heterogeneity might bring. Methods:In this study, high-throughput sequencing was applied to analyze the miRNA expression profiles in the islet cells from the pancreatic head and tail in rats. The TargetScan and miRDB databases were used to predict target genes of the differentially expressed miRNAs (DEmiRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to analysis the target genes. Then the key miRNA was verified by qRT-PCR. Result:A total of 445 miRNAs were detected in the islet cells of the pancreatic head and tail, among which 69 showed significant differences (|log2 fold change|>0.585 and P<0.05). Comparing with the pancreatic tail, 28 miRNAs were upregulated and 41 miRNAs were downregulated in the pancreatic head. Bioinformatics analysis revealed that these target genes were significantly enriched in functions such as negative regulation of cellular process, anatomical structure development, intracellular organelle, pancreatic cancer, insulin resistance, MAPK signaling, Wnt signaling, Hippo signaling. In addition, KEGG analysis of target genes showed that miR-124-3p was in several pathways, such as insulin signaling pathway, endocrine resistance, small cell lung cancer, and other pathways in cancer. qRT-PCR results showed that miR-124-3p was significantly upregulated in the pancreatic head. Conclusions:Our research exhibits novel insights on the molecular mechanisms underlying pancreatic cancer and offered potential targets for future diagnostic and therapeutic strategies. Overall design: miRNA profiles in the islet cells from the pancreatic head and tail of 24-week-old male SD rats were generated by high-throughput sequencing, in six copies, using Illumina NextSeq 500.