Transcriptome analysis reveals that hydrogen sulfide exposure suppresses cell proliferation and induces apoptosis through ciR-PTPN23/miR-15a/ E2F3 signaling in broiler thymus

The immune organs, like thymus, are one of the targets of hydrogen sulfide (H2S). Previously we reported that H2S induced the differential expression of mRNAs that implicating apoptosis in thymus, however, the roles of noncoding RNAs (ncRNAs) in H2S-induced thymus injury are still unknown. Pollution gases could alter the expression of ncRNAs, which have been shown to play important roles in many physiological and pathophysiological processes, including immune activity. This study revealed that H2S exposure induced 9 differentially expressed circRNAs and 15 differentially expressed miRNAs in chicken thymus. Furthermore, the circRNA miRNA - mRNA network was constructed. We discovered that circR-PTPN23 - miR-15a - E2F3 was involved in the cell cycle and apoptosis. Further, an in vitro H2S exposure model was established using HD11 cell line and demonstrated that H2S suppressed cell proliferation and induced apoptosis. Moreover, ciR-PTPN23 and E2F3 were downregulated, but miR-15a was upregulated in both the thymus and HD11 cell line after H2S exposure. Bioinformatics analysis revealed that ciR-PTPN23 directly bound to miR-15a and that E2F3 was the target gene of miR-15a. Knocking down ciR-PTPN23 suppressed HD11 proliferation and caused G1 arrest and apoptosis, however, this phenomenon could be partially reversed by ciR-PTPN23 overexpression or miR-15a silencing. In summary, the ciR-PTPN23 - miR-15a - E2F3 axis was involved in H2S-induced cell proliferation suppression and apoptosis.