PARP1 Regulates Cellular Processes Mediated by Exosomal miRNAs in Dental Pulp Stem Cells

Non-coding RNAs including microRNAs (miRNAs) derived from extracellular exosomes are considered as bio-markers for multiple intracellular communication pathways. Meanwhile, poly ADP-ribosylation (PARylation) catalyzed by poly (ADP-ribose) polymerase 1 (PARP1) is related to various intracellular processes. The comprehensive idea of cell-cell signaling phenomena mediated by PARP1-related exosomes remains unsolved, although individual molecules are considered to provoke disease pathogenesis and progression under aberrant regulation. In the present study, we knocked down the PARP1 gene in dental pulp stem cells (DPSCs) by gene targeting using the CRISPR-Cas9 system to determine the functions of exosomal miRNAs regulated by PARP1. The exosomes produced by PARP1-knockdown DPSCs were harvested and the miRNAs contained within these exosomes were comprehensively analyzed by next-generation sequencing. From the results, significantly altered miRNAs were picked up among the detected miRNAs. Gene ontology enrichment analyses were performed on these miRNAs to predict their cellular functions. Most of the up-regulated miRNAs after PARP1 knockdown were identified as cell proliferation-related functional non-coding RNAs, and were indicated to affect cellular processes regulating cellular senescence and differentiation. Therefore, the present findings suggest that PARP1 in DPSCs regulates cellular processes such as cell proliferation through intercellular communication mediated by exosomal miRNAs.