Dataset Information

The regulatory mechanism of LncRNA-mediated ceRNA network in osteosarcoma.

ABSTRACT: Aberrantly expressed lncRNAs have been reported to be closely related to the oncogenesis and development of osteosarcoma. However, the role of a dysregulated lncRNA-miRNA-mRNA network in osteosarcoma in the same individual needs to be further investigated. Whole transcriptome sequencing was performed on the tumour tissues and matched paratumour tissues of three patients with confirmed osteosarcoma. Two divergent lncRNA-miRNA-mRNA regulatory networks were constructed in accordance with their biological significance. The GO and KEGG analysis results of the mRNAs in the two networks revealed that the aberrantly expressed lncRNAs were involved in regulating bone growth and development, epithelial cell proliferation, cell cycle arrest and the N-terminal acetylation of proteins. The survival analysis results of the two networks showed that patients with high expression of GALNT3, FAM91A1, STC2 and SLC7A1 end in poorer prognosis. Likewise, patients with low expression of IGF2, BLCAP, ZBTB47, THRB, PKIA and MITF also had poor prognosis. A subnetwork was then constructed to demonstrate the key genes regulated by aberrantly expressed lncRNAs at the posttranscriptional level via the ceRNA network. Aberrantly expressed lncRNAs in osteosarcoma tissues regulate genes involved in cellular proliferation, differentiation, angiogenesis and the cell cycle via the ceRNA network.

SUBMITTER: Lin C

PROVIDER: S-EPMC9130241 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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The regulatory mechanism of LncRNA-mediated ceRNA network in osteosarcoma.

Lin Chengsen C Miao Jifeng J He Juliang J Feng Wenyu W Chen Xianxiang X Jiang Xiaohong X Liu Jianhong J Li Boxiang B Huang Qian Q Liao Shijie S Liu Yun Y

Scientific reports 20220524 1

Aberrantly expressed lncRNAs have been reported to be closely related to the oncogenesis and development of osteosarcoma. However, the role of a dysregulated lncRNA-miRNA-mRNA network in osteosarcoma in the same individual needs to be further investigated. Whole transcriptome sequencing was performed on the tumour tissues and matched paratumour tissues of three patients with confirmed osteosarcoma. Two divergent lncRNA-miRNA-mRNA regulatory networks were constructed in accordance with their biol ...[more]

PMID: 35610231

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Project description:Long non-coding RNAs (lncRNAs) are among the most abundant types of non-coding RNAs in the genome and exhibit particularly high expression levels in the brain, where they play crucial roles in various neurophysiological and neuropathological processes. Although ischemic stroke is a complex multifactorial disease, the involvement of brain-derived lncRNAs in its intricate regulatory networks remains inadequately understood. In this study, we established a cerebral ischemia-reperfusion injury model using middle cerebral artery occlusion (MCAO) in male Sprague-Dawley rats. High-throughput sequencing was performed to profile the expression of cortical lncRNAs post-stroke, with subsequent validation using RT-PCR and qRT-PCR. Among the 31,183 lncRNAs detected in the rat cerebral cortex, 551 were differentially expressed between the MCAO and sham-operated groups in the ipsilateral cortex (fold change ≥2.0, P < 0.05). An integrated analysis of the 20 most abundant and significantly differentially expressed lncRNAs (DELs) identified 25 core cytoplasmic DELs, which were used to construct an interaction network based on their targeting relationships. This led to the establishment of a comprehensive lncRNA-miRNA-mRNA regulatory network comprising 12 lncRNAs, 16 sponge miRNAs, and 191 target mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that differentially expressed mRNAs (DEmRNAs) were significantly enriched in stroke-related pathways. Our analysis predicted four key lncRNAs, four miRNAs, and eleven crucial mRNAs involved in post-transcriptional regulation through competing endogenous RNA (ceRNA) mechanisms. These molecules were shown to participate extensively in post-stroke processes, including angiogenesis, axonal regeneration, inflammatory responses, microglial activation, blood-brain barrier (BBB) disruption, apoptosis, autophagy, ferroptosis, and thrombocytopenia. These findings highlight the role of lncRNAs as multi-level regulators in the complex network of post-stroke mechanisms, providing novel insights into the pathophysiological processes of stroke.

Project description:BackgroundA growing body of evidence indicates that long non-coding RNAs (lncRNAs) can act as competitive endogenous RNAs (ceRNAs) to bind to microRNAs (miRNAs), thereby affecting and regulating the expression of target genes. The lncRNA-miRNA-mRNA ceRNA network has been theorized to play an indispensable role in many types of tumors. However, the role of the lncRNA-related ceRNA regulatory network in lung adenocarcinoma (LUAD) remains unclear.MethodsWe downloaded the RNAseq and miRNAseq data of LUAD from The Cancer Genome Atlas (TCGA) data portal and identified differentially expressed lncRNAs (DElncRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) between LUAD and corresponding paracancerous tissues by using the edgeR package of R software. We constructed the lncRNA-miRNA-mRNA ceRNA network by using Cytoscape (version 3.7.2) on the basis of the interaction generated from the miRcode, miRTarBase, miRDB, and TargetScan databases. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed with DAVID 6.8 bioinformatics resources and plotted by using the ggplot2 package in R. The effect of genes on LUAD prognosis was assessed by applying the survival package in R in accordance with the Kaplan-Meier curve.ResultsIn total, 1645 DElncRNAs, 117 DEmiRNAs, and 2729 DEmRNAs were identified in LUAD. The LUAD-specific ceRNA network was composed of 157 nodes and 378 edges (329 DElncRNA-DEmiRNA interactions and 49 DEmiRNA-DEmRNA interactions). GO and KEGG pathway annotations suggested that the LUAD-specific ceRNA network was related to tumor-related molecular functions and pathways. Seven lncRNAs (DISC1-IT1, SYNPR-AS1, H19, LINC00460, LINC00518, DSCR10, and STEAP2-AS1), one miRNA (hsa-mir-31), and 16 mRNAs (ATAD2, OSCAR, KIF23, E2F7, PFKP, MCM4, CEP55, CBX2, CCNE1, CLSPN, CCNB1, CDC25A, EZH2, CHEK1, SLC7A11, and PBK) were revealed to be significantly correlated with overall survival.ConclusionIn this study, we described the potential regulatory mechanism of the progression of LUAD. We proposed a new lncRNA-miRNA-mRNA ceRNA network that could help further explore the molecular mechanisms of LUAD.

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Project description:The aim of the present study was to identify the important mRNAs, micro (mi)RNAs and long non‑coding (lnc)RNAs that are associated with osteosarcoma recurrence. The GSE3905 dataset, which contains two sub‑datasets (GSE39040 and GSE39055), was downloaded from the Gene Expression Omnibus (GEO). Prognosis‑associated RNAs were identified by performing Cox regression univariate analysis and were subsequently used to construct a competing endogenous (ce)RNA regulatory network for Gene Set Enrichment Analysis (GSEA). Kaplan‑Meier survival analysis was used to determine the associations between expression levels and survival prognosis. In addition, another independent miRNA profile, GSE79181, was downloaded from GEO for validation. Among the differentially expressed RNAs, 417 RNAs (5 lncRNAs, 19 miRNAs, and 393 mRNAs) were observed to be associated with prognosis. The GSEA for the ceRNA regulatory network revealed that 'Mitogen‑activated protein kinase (MAPK) signaling pathway', 'Chemokine signaling pathway' and 'Spliceosome' were markedly associated with osteosarcoma. In addition, three lncRNAs [long intergenic non‑protein coding RNA 28 (LINC00028), LINC00323, and small nucleolar RNA host gene 1 (SNHG1)] and two miRNAs (hsa‑miR‑124 and hsa‑miR‑7) regulating three mRNAs [Ras‑related protein Rap‑1b (RAP1B), activating transcription factor 2 (ATF2) and protein phosphatase Mg2+/Mn2+ dependent 1B (PPM1B)] participated in the MAPK signaling pathway. The Kaplan‑Meier survival analysis also demonstrated that samples with lower expression levels of LINC00323 and SNHG1 had better prognosis, and samples with increased expression levels of LINC00028, hsa‑miR‑124 and hsa‑miR‑7 had better prognosis. Overexpression of RAP1B, ATF2 and PPM1B was positively associated with osteosarcoma recurrence. The roles of hsa‑miR‑124 and hsa‑miR‑7 in osteosarcoma recurrence were also validated using GSE79181. Thus, in conclusions, the three lncRNAs (LINC00028, LINC00323 and SNHG1), two miRNAs (hsa‑miR‑124 and hsa‑miR‑7) and three mRNAs (RAP1B, ATF2, and PPM1B) were associated with osteosarcoma recurrence.

Dataset Information

The regulatory mechanism of LncRNA-mediated ceRNA network in osteosarcoma.

Publications

The regulatory mechanism of LncRNA-mediated ceRNA network in osteosarcoma.

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