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Changing expression profiles of mRNA, miRNA, lncRNA, and circRNA reveal the key regulators and interaction networks of ceRNA in pulmonary fibrosis [ncRNA-seq]

ABSTRACT: Pulmonary fibrosis is a kind of interstitial lung disease with architectural remodeling of tissues and excessive matrix deposition. Apart from mRNA, microRNA, long non-coding RNA (lncRNA) and circular RNA (circRNA) could also play important roles in the regulatory processes of occurrence and progression of pulmonary fibrosis. In the present study, whole transcriptome sequencing analysis was applied to investigate the expression profiles of mRNAs, lncRNAs, circRNAs and miRNAs. After comparing bleomycin-induced pulmonary fibrosis model lung samples and controls, 286 lncRNAs, 192 mRNAs, 605 circRNAs, and 32 miRNAs were found to be differentially expressed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the potential functions of these DE mRNAs and ncRNAs. Various related GO-BP terms such as “inflammatory response”, “positive regulation of interleukin-2 biosynthetic process”, “Regulation of actin cytoskeleton”, “Notch signaling pathway”, “negative regulation of cellular response to vascular endothelial growth factor stimulus”, and KEGG signal pathways such as “Wnt signaling pathway”, “TNF signaling pathway”, “MAPK signaling pathway”, “Regulation of actin cytoskeleton” were enriched implying potential roles in regulatory process. In addition, two co-expression networks (lncRNA-miRNA-mRNA, circRNA-miRNA-mRNA) were also constructed to understand the internal regulating relationships of these mRNAs and ncRNAs. Our study provides a systematic perspective on the potential functions of these DE mRNAs and ncRNAs during PF process, and could help pave the way for effective therapeutics for this devastating and complex disease.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE153278 | GEO | 2020/08/21

REPOSITORIES: GEO

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Project description:It has been reported that circular RNA (circRNA) is associated with human cancer. However, few studies have been reported in active pulmonary tuberculosis (APTB). The global circRNA expression was detected in the peripheral blood mononuclear cells (PBMCs) of APTB patients (n=5) and healthy controls (HC) (n=5) by using high-throughput sequencing. According to the systematical bioinformatics analysis, the basic content of circRNAs and their fold changes in the two groups were calculated. We selected 6 significant differentially expressed circRNAs, hsa_circ_0005836, hsa_circ_0009128, hsa_circ_0003519, hsa_circ_0023956, hsa_circ_0078768, and hsa_circ_0088452 and validated the expression in PBMCs from APTB (n=10) and HC (n=10) by real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs). Further, the verification of these specific circRNAs (hsa_circ_0005836 and hsa_circ_0009128) between APTB (n=34) and HC (n=30) in PBMCs was also conducted by qRT-PCRs. The RNA-seq data showed the significant differential expression of the 523 circRNAs between the APTB and HC groups (199 circRNAs were significantly up-regulated and 324 circRNAs were down-regulated). Hsa_circ_0005836 and hsa_circ_0009128 expression was significantly down-regulated in the PBMCs of APTB (P< 0.05) in the samples of APTB compared to HC in our study. The gene ontology based enrichment analysis of the circRNA-miRNA-mRNAs network showed that cellular catabolic process (P=7.10E-08), regulation of metabolic process (P=2.10E-06), catalytic activity (P=3.67E-08), protein binding (P=1.71E-07), cell part (P=3.46E-06), intracellular part (P=1.71E-07), and intracellular (P=3.67E-08) were recognized in the comparisons between APTB and HC. Based on KEGG analysis, HTLV-I infection, regulation of actin cytoskeleton, neurotrophin signaling pathway and mTOR signaling pathway were relevant during tuberculosis bacillus infection. We found for the first time that hsa_circ_0005836 and hsa_circ_0009128 were significantly down-regulated in the PBMCs of APTB compared with HC. Our findings indicate hsa_circ_0005836 might serve as a novel potential biomarker for TB infection.

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Changing expression profiles of mRNA, miRNA, lncRNA, and circRNA reveal the key regulators and interaction networks of ceRNA in pulmonary fibrosis [ncRNA-seq]

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