Dataset Information

Identification of Differentially Expressed Circular RNAs as miRNA Sponges in Lung Adenocarcinoma.

ABSTRACT:

Background

Circular RNAs (circRNAs) may function as the decoys for microRNAs (miRNAs) or proteins, the templates for translation, and the sources of pseudogene generation. The purpose of this study is to determine the diagnostic circRNAs, which are related to lung adenocarcinoma (LUAD), that adsorb miRNAs on the basis of the competing endogenous RNA (ceRNA) hypothesis.

Methods

The differentially expressed circRNAs (DEcircRNAs) in LUAD were revealed by the microarray data (GSE101586 and GSE101684) that were obtained from the Gene Expression Omnibus (GEO) database. The miRNAs that were targeted by the DEcircRNAs were predicted with the CircInteractome, and the target mRNAs of the miRNAs were found by the miRDB and the TargetScan. The ceRNA network was built by the Cytoscape. The potential biological roles and the regulatory mechanisms of the circRNAs were investigated by the Gene Ontology (GO) enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The expression of the host genes of circRNAs was examined by the Ualcan. The survival analysis was performed by the Kaplan-Meier plotter.

Results

In comparison with normal lung tissues, LUAD tissues contained 7 overlapping cancer-specific DEcircRNAs with 294 miRNA response elements (MREs). Among the 7 DEcircRNAs, 3 circRNAs (hsa_circ_0072088, hsa_circ_0003528, and hsa_circ_0008274) were upregulated and 4 circRNAs (hsa_circ_0003162, hsa_circ_0029426, hsa_circ_0049271, and hsa_circ_0043256) were downregulated. A circRNA-miRNA-mRNA regulatory network, which included 33 differentially expressed miRNAs (DEmiRNAs) and 2007 differentially expressed mRNAs (DEmRNAs), was constructed. These mRNAs were enriched in the biological function of cell-cell adhesion, response to hypoxia, and stem cell differentiation and were involved in the PI3K-Akt signaling, HIF-1 signaling, and cAMP signaling pathways.

Conclusion

Our results indicated that 7 DEcircRNAs could have diagnostic value for LUAD. Additionally, the circRNAs-mediated ceRNA network might provide a novel perspective into unraveling the pathogenesis and progression of LUAD.

SUBMITTER: Liu Y

PROVIDER: S-EPMC8448594 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Allergic asthma is one of the most common allergic diseases; however, the mechanisms underlying its development have yet to be fully elucidated. Although allergic diseases are inheritable, genetic variance alone cannot explain the notable increase in the prevalence of allergic diseases over a short period of time in recent decades. Recently, research focus has been shifting to epigenetic factors, such as non‑coding RNAs. Circular RNAs (circRNAs) are involved in the pathogenesis of various diseases. The aim of the present study was to further elucidate the etiology of allergic asthma by analyzing aberrantly expressed circRNAs in a murine asthma model. A mouse model of house dust mite allergen‑induced asthma was established, and the qualified libraries were sequenced using next‑generation sequencing. The expression levels of circRNAs were validated by reverse transcription‑quantitative PCR (RT‑qPCR) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for biological pathway classification and enrichment analysis of the aberrantly expressed circRNAs. In addition, the interaction network of the differentially expressed circRNAs and microRNAs (miRNAs) was constructed using Cytoscape. By next‑generation sequencing, a total of 150 circRNAs were revealed to be upregulated and 130 were downregulated in the murine asthma model group compared with in the control group. GO and KEGG analyses demonstrated that the differentially expressed circRNAs were mainly involved in processes such as 'autoimmune disease', 'cell adhesion molecules (CAMs)' and 'endocytosis', among others. The expression levels of six circRNAs, namely three upregulated (circ_0000909, circ_0000629 and circ_0000455) and three downregulated (circ_0001454, circ_0000723 and circ_0001389) circRNAs, were validated by RT‑qPCR. In conclusion, the analyses suggested that circRNAs performed critical functions via endocytosis (such as macrophage endocytosis), cell adhesion molecules and lipid metabolism in allergic asthma. The interaction network revealed that certain miRNAs that may serve a role in asthma could be regulated by the differentially expressed circRNAs.