Dataset Information

A novel lncRNA-miRNA-mRNA network analysis identified the hub lncRNA RP11-159F24.1 in the pathogenesis of papillary thyroid cancer.

ABSTRACT: Papillary thyroid cancer (PTC) is one of the most common cancers worldwide, and its carcinogenesis is influenced by a complex network of gene interactions. In this study, the microarray expression profile was re-annotated into a lncRNA-mRNA biphasic profile. LncRNA-mRNA interactions were confirmed by established miRNA-RNA data and hypergeometric test. Then, a PTC-related lncRNA-miRNA-mRNA network (PTCRN) was constructed by integrating differentially expressed genes with the RNA-RNA networks. The new network consisted of 21 lncRNAs, 241 mRNAs and 803 edges. To prioritize PTC-related genes, we performed topological analysis and random walk with restart (PWR) algorithm analysis of PTCRN. Both analyses identified lncRNA RP11-159F24.1 as a hub node in the network, which could interact with 47 mRNAs by sponging miR-485. In functional enrichment analysis, these interacting mRNAs were associated with the pathways in cancer. In validation, RP11-159F24.1 (up-regulated; P = 0.0013) showed an opposite expression pattern with its target miR-485 (down-regulated; P = 0.0013) in PTC, indicating that the RP11-159F24.1/miR-485/mRNAs axis might play an important role in the development of PTC. In conclusion, this study has constructed a PTC-related lncRNA-miRNA-mRNA network and identified the hub lncRNA RP11-159F24.1 in the tumorigenesis, which provided novel insights to explore the underlying mechanism of PTC.

SUBMITTER: Jiang W

PROVIDER: S-EPMC6308055 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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A novel lncRNA-miRNA-mRNA network analysis identified the hub lncRNA RP11-159F24.1 in the pathogenesis of papillary thyroid cancer.

Jiang Wei W Zhan Hua H Jiao Yanyan Y Li Sha S Gao Weixu W

Cancer medicine 20181126 12

Papillary thyroid cancer (PTC) is one of the most common cancers worldwide, and its carcinogenesis is influenced by a complex network of gene interactions. In this study, the microarray expression profile was re-annotated into a lncRNA-mRNA biphasic profile. LncRNA-mRNA interactions were confirmed by established miRNA-RNA data and hypergeometric test. Then, a PTC-related lncRNA-miRNA-mRNA network (PTCRN) was constructed by integrating differentially expressed genes with the RNA-RNA networks. The ...[more]

PMID: 30474931

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Project description:Long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and progression of different cancers and they have been potential biomarkers for cancer diagnosis and prognosis. As the most common endocrine malignancy, precise diagnosis and prognosis of papillary thyroid cancer (PTC) is of great clinical significance. Here, we aim to identify new hub lncRNAs for marking PTC and constructed prognostics signatures based on lncRNA- miRNA-mRNA competing endogenous RNAs (ceRNA) network to predict overall survival (OS) and disease-free survival (DFS) respectively. Five reliable hub lncRNAs were identified by integrating differential genes of four Gene Expression Omnibus (GEO) gene chips using the RobustRankAggreg (RRA) method. Based on differential analyses and interaction prediction, a lncRNA-mRNA co-expression network and a lncRNA-miRNA-mRNA ceRNA network were established. Then a comprehensive function characterization of the five hub lncRNAs was performed, including validation dataset testing, receiver operating characteristic (ROC) curve analysis, and functional analysis on two networks. All results suggest that these five hub lncRNAs could be potential biomarkers for marking PTC. The ceRNA network was used to identify RNAs which were associated with PTC prognosis. Two prognostic signatures were developed using univariate and step-wise multivariate Cox regression analyses and both of them were independent prognostic indicators for PTC OS and DFS. Tumor microenvironment difference analysis between high and low-risk patients showed that dendritic cells activated and macrophages M0 may be a possible target for immunotherapy of PTC. In addition, disclosing the potential drugs that may reverse the expression of hub genes may improve the prognosis of patients with PTC. Here, connectivity map (CMap) analysis indicates that three bioactive chemicals (pioglitazone, benserazide, and SB-203580) are promising therapeutic agents for PTC. So, the paper presents a comprehensive study on diagnosis, prognosis, and potential drug screening for PTC based on the five hub lncRNAs identified by us.

Project description:IntroductionPolycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder prevalent among women of reproductive age. Recent studies show that autophagy participated in the pathogenesis of PCOS, including anovulation, hyperandrogenism, and metabolic disturbances. This study was designed to screen autophagy-related genes (ATGs) that may play a pivotal role in PCOS, providing potential biomarkers and identifying new molecular subgroups for therapeutic intervention.MethodsGene expression profiles of the PCOS and control samples were obtained from the publicly available Gene Expression Omnibus database. The gene lists of ATGs from databases were integrated. Then, the weighted gene co-expression network analysis was conducted to obtain functional modules and construct a multifactorial co-expression network. Gene Ontology and KEGG pathway enrichment analyses were performed for further exploration of ATG's function in the key modules. Differentially expressed ATGs were identified and validated in external datasets with the Limma R package. To provide guidance on PCOS phenotyping, the dysfunction module consists of a co-expression network mapped to PCOS patients. A PCOS-Autophagy-related co-expression network was established using Cytoscape, followed by identifying molecular subgroups using the Limma R package. ps. RNA-sequencing analysis was used to confirm the differential expression of hub ATGs, and the diagnostic value of hub ATGs was assessed by receiver operating characteristic curve analysis.ResultsThree modules (Brown, Turquoise, and Green) in GSE8157, three modules (Blue, Red, and Green) in GSE43264, and four modules (Blue, Green, Black, and Yellow) in GSE106724 were identified to be PCOS-related by WGCNA analysis. 29 ATGs were found to be the hub genes that strongly correlated with PCOS. These hub ATGs were mainly enriched in autophagy-related functions and pathways such as autophagy, endocytosis, apoptosis, and mTOR signaling pathways. The mRNA-miRNA-lncRNA multifactorial network was successfully constructed. And three new molecular subgroups were identified via the K-means algorithm.DiscussionWe provide a novel insight into the mechanisms behind autophagy in PCOS. BRCA1, LDLR, MAP1B, hsa-miR-92b-3p, hsa-miR-20b-5p, and NEAT1 might play a considerably important role in PCOS dysfunction. As a result, new potential biomarkers can be evaluated for use in PCOS diagnosis and treatment in the future.

Dataset Information

A novel lncRNA-miRNA-mRNA network analysis identified the hub lncRNA RP11-159F24.1 in the pathogenesis of papillary thyroid cancer.

Publications

A novel lncRNA-miRNA-mRNA network analysis identified the hub lncRNA RP11-159F24.1 in the pathogenesis of papillary thyroid cancer.

Similar Datasets

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