Liu Yan-Ping, Cai Ying, Lei Yuan-di, Yuan Xiao-Yan, Wang Ye, Yi Shan, Li Xun-Ya, Huang Lian, Long Ding-Xin, Zhang Zhao-Hui
Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.
Toxicol Res (Camb). 2021 Aug 27;10(5):1013-1021. doi: 10.1093/toxres/tfab086. eCollection 2021 Oct.
Circular RNAs (circRNAs), is a novel type of endogenous non-coding RNAs (ncRNAs) participated in the pathogenesis of many diseases. Beryllium is one of the carcinogenesis elements. However, the mechanism and function of circRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO) was rarely reported. Therefore, the high-throughput RNA sequencing analysis was performed to detect the circRNA profiles between control groups and BeSO-induced groups. Furthermore, circRNA-miRNA-mRNA network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and PPI network analysis were used for bioinformatics analysis. CircRNA sequencing analysis revealed that 36 circRNAs were up-regulated and 35 circRNAs were down-regulated in the BeSO-exposed groups. The selected circRNAs were verified by real-time fluorescent quantitative PCR (qRT-PCR). Hsa_circ_0004214 and hsa_circ_0003586 were validated to be up-regulated, hsa_circ_0047958, hsa_circ_0001944, and hsa_circ_0008982 were down-regulated. The circRNA-miRNA-mRNA network annotated the key signaling pathway including cellular senescence, TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway, and Hippo signaling pathway. The PPI network indicated the most circRNAs might participate in the BeSO toxicity by acting as a sponge for the miR-663b through JAK-STAT signaling pathway. In summary, our study suggests that circRNAs may play roles in the mechanism of beryllium toxicity.
环状RNA(circRNAs)是一类新型的内源性非编码RNA(ncRNAs),参与多种疾病的发病机制。铍是致癌元素之一。然而,硫酸铍(BeSO)诱导人支气管上皮细胞(16HBE)中circRNAs的机制和功能鲜有报道。因此,进行了高通量RNA测序分析,以检测对照组和BeSO诱导组之间的circRNA谱。此外,还利用circRNA- miRNA- mRNA网络、基因本体论(GO)、京都基因与基因组百科全书(KEGG)通路分析以及蛋白质-蛋白质相互作用(PPI)网络分析进行生物信息学分析。circRNA测序分析显示,在BeSO暴露组中,36种circRNAs上调,35种circRNAs下调。通过实时荧光定量PCR(qRT-PCR)对所选的circRNAs进行了验证。hsa_circ_0004214和hsa_circ_0003586被验证为上调,hsa_circ_0047958、hsa_circ_0001944和hsa_circ_0008982被下调。circRNA- miRNA- mRNA网络注释了关键信号通路,包括细胞衰老、TNF信号通路、NF-κB信号通路、HIF-1信号通路和Hippo信号通路。PPI网络表明,大多数circRNAs可能通过JAK-STAT信号通路作为miR-663b的海绵参与BeSO毒性作用。总之,我们的研究表明circRNAs可能在铍毒性机制中发挥作用。