Competitive endogenous RNA (ceRNA) regulation network of lncRNA-miRNA-mRNA during the process of the nickel-induced steroidogenesis disturbance in rat Leydig cells

Nickel (Ni) is a ubiquitous environmental pollutant, which can disrupt the production of steroid in rat Leydig cells. Steroidogenesis can be affected by non-coding RNAs (ncRNAs), which operate in normal physiological processes. To date, however, very few studies have focused on whether ncRNAs are involved in Ni-induced steroidogenesis disturbance. The present study was designed to investigate the impact of NiSO4 on the regulation of RNA networks including long non-coding RNA (lncRNA), microRNA (miRNA), and mRNA in rat Leydig cells. After treatment with 1000 mu mol/L NiSO4 for 24 h, 372 lncRNAs, 27 miRNAs (fold change > 2, p < .05) and 3666 mRNAs (fold change > 2, p < .01, and FDR < 0.01) were identified to be markedly altered by high-throughput sequencing analysis in rat Leydig cells. Functional analysis showed that the differentially expressed mRNAs were annotated into some steroid-related pathways. A dysregulated competing endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA was constructed based on bioinformatic analysis. Furthermore, a ceRNA network related to steroidogenesis was selected to analyze further and after the validation by qRT-PCR. The LOC102549726/miR-760-3/Atf6, LOC102549726/miR-760-3p/Etsl, LOC102549726/miR-760-3p/Sikl and AABR07037489.1/miR-708-5p/MAPK14 ceRNA networks were eventually confirmed. Collectively, our study provided a systematic perspective on the potential role of ncRNAs in steroidogenesis disturbance induced by Ni in rat Leydig cells.