A novel circular RNA (hsa_circ_0059930)-mediated miRNA-mRNA axis in the lipopolysaccharide-induced acute lung injury model of MRC-5 cells

脂多糖诱导的MRC-5细胞急性肺损伤模型中一种新的环状RNA(hsa_circ_0059930)介导的miRNA-mRNA轴

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作者:Jianhua Han, Shigeng Li, Yawei Feng, Yufeng He, Weilong Hong, Zhiqiang Ye

Abstract

Circular RNA (circRNA) is a class of newly discovered endogenous non-coding RNA with closed circular structure. Some circRNAs have been reported to be closely associated with acute lung injury (ALI). While the expression profile of circRNAs in lipopolysaccharide (LPS)-induced ALI and the underlying roles are still not completely clear. The LPS-induced ALI model of MRC-5 cells was first established, and the expression profiles of circRNAs and mRNAs in LPS-induced MRC-5 cells were confirmed through RNA sequencing analysis. Gene Ontologyanalysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were also applied to predict the latent functions and pathways of the differential mRNAs. After hsa_circ_0059930 knockdown, the proliferation and apoptosis of MRC-5 cells were identified by CCK-8, flow cytometer, and western blot assays. And we predicted the network analysis of hsa_circ_0059930. We testified that LPS could markedly prevent proliferation and induce apoptosis of MRC-5 cells. We discovered a total of 820 differential circRNAs (560 upregulated and 260 downregulated circRNAs) and 484 differential mRNAs (240 upregulated and 244 downregulated mRNAs) in LPS-induced MRC-5 cells. Besides, hsa_circ_0059930 was identified to be significantly upregulated in LPS-induced MRC-5 cells, and knockdown of hsa_circ-0059930 could notably accelerate proliferation and suppress apoptosis of LPS-mediated MRC-5 cells. Moreover, through the network analysis of hsa_circ_0059930, we preliminarily screened the potential regulatory axis hsa_circ_0059930/hsa-miR-382-5p/Topoisomerase 1 (TOP1) in LPS-induced ALI. Our data contribute to understand the importance of circRNAs and mRNAs in LPS-induced ALI. We also provided many hsa_circ_0059930-mediated microRNA (miRNA)-mRNA axis, especially hsa_circ_0059930/hsa-miR-382-5p/TOP1 in LPS-induced ALI.

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