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Identification and validation of long non-coding RNA associated ceRNAs in intrauterine adhesion.

ABSTRACT: Intrauterine adhesion (IUA) is an endometrial fibrotic disease with unclear pathogenesis. Increasing evidence suggested the important role of competitive endogenous RNA (ceRNA) in diseases. This study aimed to identify and verify the key long non-coding RNA (lncRNA) associated-ceRNAs in IUA. The lncRNA/mRNA expression file was obtained by transcriptome sequencing of IUA and normal samples. The microRNAs expression date was downloaded from the Gene Expression Omnibus database. Differential expressions of mRNAs, lncRNAs and miRNAs were analyzed using the DESeq2 (2010) R package. Protein interaction network was constructed to explore hub genes. TargetScan and miRanda databases were used to predicate the interaction. Enrichment analysis in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were performed to identify the biological functions of ceRNAs. Regression analysis of ceRNAs' expression level was performed. There were 915 mRNAs and 418 lncRNAs differentially expressed. AURKA, CDC20, IL6, ASPM, CDCA8, BIRC5, UBE2C, H2AFX, RRM2 and CENPE were identified as hub genes. The ceRNAs network, including 28 lncRNAs, 28 miRNAs, and 299 mRNAs, was constructed. Regression analysis showed a good positive correlation between ceRNAs expression levels (r > 0.700, p < 0.001). The enriched functions include ion transmembrane transport, focal adhesion, cAMP signaling pathway and cGMP-PKG signaling pathway. The novel lncRNA-miRNA-mRNA network in IUA was excavated. Crucial lncRNAs such as ADIRF-AS1, LINC00632, DIO3OS, MBNL1-AS1, MIR1-1HG-AS1, AC100803.2 was involved in the development of IUA. cGMP-PKG signaling pathway and ion transport might be new directions for IUA pathogenesis research.

SUBMITTER: Zhang J

PROVIDER: S-EPMC8805920 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although multiple efforts have been made to understand the development of HCC, morbidity, and mortality rates remain high. In this study, we aimed to discover the mRNAs and long non-coding RNAs (lncRNAs) that contribute to the progression of HCC. We constructed a lncRNA-related competitive endogenous RNA (ceRNA) network to elucidate the molecular regulatory mechanism underlying HCC.MethodsA microarray dataset (GSE54238) containing information about both mRNAs and lncRNAs was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs (DElncRNAs) in tumor tissues and non-cancerous tissues were identified using the limma package of the R software. The miRNAs that are targeted by DElncRNAs were predicted using miRcode, while the target mRNAs of miRNAs were retrieved from miRDB, miRTarBas, and TargetScan. Functional annotation and pathway enrichment of DEGs were performed using the EnrichNet website. We constructed a protein-protein interaction (PPI) network of DEGs using STRING, and identified the hub genes using Cytoscape. Survival analysis of the hub genes and DElncRNAs was performed using the gene expression profiling interactive analysis database. The expression of molecules with prognostic values was validated on the UALCAN database. The hepatic expression of hub genes was examined using the Human Protein Atlas. The hub genes and DElncRNAs with prognostic values as well as the predictive miRNAs were selected to construct the ceRNA networks.ResultsWe found that 10 hub genes (KPNA2, MCM7, CKS2, KIF23, HMGB2, ZWINT, E2F1, MCM4, H2AFX, and EZH2) and four lncRNAs (FAM182B, SNHG6, SNHG1, and SNHG3) with prognostic values were overexpressed in the hepatic tumor samples. We also constructed a network containing 10 lncRNA-miRNA-mRNA pathways, which might be responsible for regulating the biological mechanisms underlying HCC.ConclusionWe found that the 10 significantly overexpressed hub genes and four lncRNAs were negatively correlated with the prognosis of HCC. Further, we suggest that lncRNA SNHG1 and the SNHG3-related ceRNAs can be potential research targets for exploring the molecular mechanisms of HCC.

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Identification and validation of long non-coding RNA associated ceRNAs in intrauterine adhesion.

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