Abstract
BackgroundPancreatic cancer is one of the most malignant tumors. However, radiotherapy can lead to tumor recurrence, which is caused by the residual surviving cells repopulation stimulated by some molecular released from dying cells. Exosomes may mediate cell-cell communication and transfer kinds of signals from the dying cells to the surviving cells for stimulating tumor repopulation. Circular RNAs (circRNAs) may be one vital kind of exosomal cargos involving in modulating cancer cell repopulation.MethodsNext generation sequencing (NGS) and bioinformatics were performed to analyze and annotate the expression and function of exosome-derived circRNAs in pancreatic cancer cells after radiation. Four circRNAs were chosen for qRT-PCR analysis to validate the sequencing results.ResultsIn this study, 3580 circRNAs were annotated in literatures and circBase among 12,572 identified circRNAs. There were 196 filtered differentially expressed circRNAs (the up-regulation and down-regulation respectively is 182 and 14, fold change > 2, p-value < 0.05). Regulation of metabolic process and lysine degradation were the main enriched biological processes and pathway according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.ConclusionsThe hsa_circ_0002130-hsa_miR_4482-3p-NBN interaction network suggested potential sponging miRNA and target mRNA. Our results provided potential functions of circRNAs to explore molecular mechanisms and therapeutic targets in pancreatic cancer cell repopulation upon irradiation.
Highlights
Pancreatic cancer is one of the most malignant tumors
Exosome characterization and RNA-seq library construction Exosomes secreted by 4 kinds of pancreatic cancer cells (PANC-1, SW1990, MIA Paca-2, BxPC-3) that were treated with or without irradiation were obtained by ultracentrifugation
Under transmission electron microscope (TEM), exosomes were irregular spheres ranging of 30–100 nm in diameter (Fig. 2a, b), which agreed well with the references [9,10,11]
Summary
Radiotherapy can lead to tumor recurrence, which is caused by the residual surviving cells repopulation stimulated by some molecular released from dying cells. Exosomes may mediate cell-cell communication and transfer kinds of signals from the dying cells to the surviving cells for stimulating tumor repopulation. Circular RNAs (circRNAs) may be one vital kind of exosomal cargos involving in modulating cancer cell repopulation. Pancreatic cancer is a highly fatal disease, which morbidity is almost the same as the mortality. The high mortality of pancreatic cancer might partly ascribe to the lack of effective strategies. Radiotherapy should be an optimal choice for those regional unresectable disease without detectable metastasis in most cancers. Modality, fraction size, and sequencing, as well as in combination with other treatment strategies such as immunotherapy have been largely studied [3].
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