A Survival-Related Competitive Endogenous RNA Network of Prognostic lncRNAs, miRNAs, and mRNAs in Wilms Tumor

Wilms tumor (WT) commonly occurs in infants and children. We evaluated clinical factors and the expression of multiple RNAs in WT samples in the TARGET database. Eight long non-coding RNAs (lncRNAs; AC079310.1, MYCNOS, LINC00271, AL445228.3, Z84485.1, AC091180.5, AP002518.2, and AC007879.3), two microRNAs (miRNAs; hsa-mir-152 andhsa-mir-181a), and nine messenger RNAs (mRNAs; TCTEX1D4, RNF133, VRK1, CCNE1, HEY1, C10orf71, SPRY1, SPAG11A, and MAGEB18) were screened from differentially expressed RNAs and used to construct predictive survival models. These models showed good prognostic ability and were highly correlated with tumor stage and histological classification. Additionally, survival-related ceRNA network was constructed using 35 RNAs (15 lncRNAs, eight miRNAs, and 12 mRNAs). KEGG pathway analysis suggested the “Wnt signaling pathway” and “Cellular senescence” as the main pathways. In conclusion, we established a multinomial predictive survival model and a survival-related ceRNA network, which provide new potential biomarkers that may improve the prognosis and treatment of WT patients.

Download Full-text

Roles of ncRNAs as ceRNAs in Gastric Cancer

Genes ◽

10.3390/genes12071036 ◽

2021 ◽

Vol 12 (7) ◽

pp. 1036

Author(s):

Junhong Ye ◽

Jifu Li ◽

Ping Zhao

Keyword(s):

Gastric Cancer ◽

Research Strategy ◽

Circular Rnas ◽

Messenger Rnas ◽

Cerna Network ◽

Degree Of Malignancy ◽

High Degree ◽

Competitive Endogenous Rna ◽

Made In

Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC’s mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC’s ceRNA network.

Download Full-text

Comprehensive Analysis of a Long Noncoding RNA-Associated Competing Endogenous RNA Network in Wilms Tumor

Cancer Control ◽

10.1177/1073274820936991 ◽

2020 ◽

Vol 27 (2) ◽

pp. 107327482093699

Author(s):

Feng Zhang ◽

Liping Zeng ◽

Qinming Cai ◽

Zihao Xu ◽

Ruida Liu ◽

...

Keyword(s):

Long Noncoding Rna ◽

Noncoding Rna ◽

Wilms Tumor ◽

Interaction Network ◽

Tumor Stage ◽

Messenger Rnas ◽

Competing Endogenous Rna ◽

Ontology Term ◽

Normal Tissues ◽

Pathway Analyses

Long noncoding RNA (lncRNA) plays crucial roles in various biological processes of different cancers, especially acting as a competing endogenous RNA (ceRNA). However, the role of lncRNA-mediated ceRNA in Wilms tumor (WT), which is the most common malignant kidney cancer in children, remains unknown. In present study, RNA sequence profiles and clinical data of 125 patients with WT consisting of 119 tumor and 6 normal tissues from Therapeutically Applicable Research To Generate Effective Treatments database were analyzed. A total of 1833 lncRNAs, 156 microRNAs (miRNAs), and 3443 messenger RNAs (mRNAs) were identified as differentially expressed (DE) using “DESeq2” package. The lncRNA-miRNA-mRNA ceRNA regulatory network involving 748 DElncRNAs, 33 DEmiRNAs, and 189 DEmRNAs was constructed based on miRcode, Targetscan, miRTarBase, and miRDB database. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that DEmRNAs were mainly enriched in cell proliferation-related processes and tumor-related pathways, respectively, and 13 hub genes were identified by a protein–protein interaction network. Survival analysis detected 48 lncRNAs, 7 miRNAs, and 16 mRNAs to have significant impact on the overall survival of patients with WT. Additionally, we found that 6 DElncRNAs with potential prognostic value were correlated with tumor stage ( DENND5B-AS1) and histologic classification ( TMPO-AS1, RP3-523K23.2, RP11-598F7.3, LAMP5-AS1, and AC013275.2) of patients with WT. Our research provides a great insight into understanding the molecular mechanism underlying occurrence and progression of WT, as well as the potential to develop targeted therapies and prognostic biomarkers.

Download Full-text

Competitive Endogenous RNA (ceRNA) Regulation Network of lncRNA–miRNA–mRNA in Wilms tumor

10.21203/rs.2.11185/v2 ◽

2019 ◽

Author(s):

fucai tang ◽

zechao Lu ◽

jiamin wang ◽

zhibiao Li ◽

weijia Wu ◽

...

Keyword(s):

Overall Survival ◽

Regulatory Network ◽

Wilms Tumor ◽

R Package ◽

Functional Enrichment ◽

Differentially Expressed ◽

Survival Prognosis ◽

Cerna Network ◽

Mechanism Of Interaction ◽

Competitive Endogenous Rna

Abstract Background: Competitive endogenous RNA (ceRNA) have revealed a new mechanism of interaction between RNAs. However, such comprehension of the ceRNA regulatory network in wilms tumor remains limited. Methods: Raw RNA sequencing profiles regarding mRNAs, miRNAs and lncRNAs on wilms tumor samples and normal samples were obtained from Therapeutically Applicable Research to Generate Effective Treatment (TARGET). EdgeR package was applied to identify differentially expressed lncRNAs, miRNAs and mRNAs. Functional enrichment analyses were conducted via DAVID database and the ClusterProfile R package. The lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape according to the identified lncRNAs–miRNAs and miRNAs–mRNAs interactions. Subsequently, correlation between ceRNA network and overall survival prognosis were analyzed. Results: A total of 2,037 lncRNAs, 154 miRNAs and 3,609 mRNAs were identified as differentially expressed RNAs in wilms tumor. 205 lncRNAs, 26 miRNAs and 143 mRNAs were included in ceRNA regulatory network. Analysis results showed that 14 out of the 205 lncRNAs, 1 out of 26 miRNAs and 8 out of 143 mRNAs were associated with overall survival in Wilms tumor patients (P < 0.05). Conclusions: CeRNA networks played an important role in Wilms tumor. This might provide effective bioinformatics basis and novel insights for further understanding of the mechanisms underlying Wilms tumor.

Download Full-text

KCNMB2-AS1 Promotes Bladder Cancer Progression Through Sponging miR-374a-3p to Upregulate S100A10

Frontiers in Genetics ◽

10.3389/fgene.2021.655569 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jianhua Zhu ◽

Yan Huang ◽

Yong Zhang ◽

Rongfu Huang ◽

Chunmei Huang

Keyword(s):

Bladder Cancer ◽

Cancer Progression ◽

Crucial Role ◽

Migration And Invasion ◽

Non Coding Rnas ◽

Highly Correlated ◽

Underlying Mechanisms ◽

Competitive Endogenous Rna

Long non-coding RNAs (lncRNAs) have been reported to play a crucial role in the pathogenesis of numerous cancers. However, the function of lncRNA KCNMB2-AS1 in bladder cancer (BC) remains unclear. In the present study, we aimed to explore the role and underlying mechanisms of KCNMB2-AS1 in bladder cancer progression. We found that lncRNA KCNMB2-AS1 was significantly upregulated both in BC tissues and cell lines, the expression level was highly correlated with pathological TNM stage. Functionally, knockdown of lncRNA KCNMB2-AS1 dramatically inhibited the proliferation, migration, and invasion and of BC cells in vitro, and suppressed tumor growth in vivo. Mechanistically, lncRNA KCNMB2-AS1 could function as a competitive endogenous RNA (ceRNA) through direct sponging miR-374a-3p, which regulated the expression of S100A10. In conclusion, our results demonstrated that lncRNA KCNMB2-AS1 can promote the progression of bladder cancer through regulation of miR-374a-3p/S100A10.

Download Full-text

Competitive Endogenous RNA (ceRNA) Regulation Network of lncRNA–miRNA–mRNA in wilms tumor

10.21203/rs.2.11185/v1 ◽

2019 ◽

Author(s):

fucai tang ◽

zechao Lu ◽

jiamin wang ◽

zhibiao Li ◽

weijia Wu ◽

...

Keyword(s):

Overall Survival ◽

Regulatory Network ◽

Wilms Tumor ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Survival Prognosis ◽

Cerna Network ◽

Competitive Endogenous Rna

Abstract Background Competitive endogenous RNA (ceRNA) have revealed a new mechanism of interaction between RNAs. However, such comprehension of the ceRNA regulatory network in wilms tumor remains limited. Methods Raw RNA sequencing profiles regarding mRNAs, miRNAs and lncRNAs on wilms tumor samples and normal samples were obtained from Therapeutically Applicable Research to Generate Effective Treatment (TARGET). EdgeR package was applied to identify differentially expressed lncRNAs, miRNAs and mRNAs. Functional enrichment analysis were conducted via DAVID database and the ClusterProfile R package. The lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape according to the identified lncRNAs–miRNAs and miRNAs–mRNAs interactions. Subsequently, correlation between ceRNA network and overall survival prognosis were analyzed. Results A total of 2,037 lncRNAs, 154 miRNAs and 3,609 mRNAs were identified as differentially expressed RNAs in wilms tumor. 205 lncRNAs, 26 miRNAs and 143 mRNAs were included in ceRNA regulatory network. Analysis results showed that 14 out of the 205 lncRNAs, 1 out of 26 miRNAs and 8 out of 143 mRNAs were associated with overall survival in wilms tumor patients (P < 0.05). Conclusions CeRNA networks played an important role in wilms tumor. This might provide effective bioinformatics basis and novel insights for further understanding of the mechanisms underlying wilms tumor.

Download Full-text

Competitive Endogenous RNA (ceRNA) Regulation Network of lncRNA-miRNA-mRNA in Wilms tumor

10.21203/rs.2.11185/v3 ◽

2019 ◽

Author(s):

fucai tang ◽

zechao Lu ◽

jiamin wang ◽

zhibiao Li ◽

weijia Wu ◽

...

Keyword(s):

Overall Survival ◽

Transcription Factor ◽

Regulatory Network ◽

Wilms Tumor ◽

Expression Profiles ◽

Functional Enrichment ◽

Differentially Expressed ◽

Proximal Promoter ◽

Cerna Network ◽

Competitive Endogenous Rna

Abstract Background: Competitive endogenous RNA (ceRNA) have revealed a new mechanism of interaction between RNAs. However, such comprehension of the ceRNA regulatory network in Wilms tumor remains limited.Methods: The expression profiles regarding mRNAs, miRNAs and lncRNAs on Wilms tumor samples and normal samples were obtained from Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database. EdgeR package was applied to identify differentially expressed lncRNAs, miRNAs and mRNAs. Functional enrichment analyses via the ClusterProfile R package was done. following which the lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape . Subsequently, correlation between ceRNA network and overall survival prognosis were analyzed. Results: A total of 2,037 lncRNAs, 154 miRNAs and 3,609 mRNAs were identified as differentially expressed RNAs in Wilms tumor. 205 lncRNAs, 26 miRNAs and 143 mRNAs were included in ceRNA regulatory network. The result of Gene Ontology analysis revealed that DEGs were enriched mainly in response to mechanical stimulus, transcription factor complex, and transcription factor activity (RNA polymerase II proximal promoter sequence-specific DNA binding). The result of the Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DEGs were enriched mainly in cell cycle. Survival analysis results showed that 14 out of the 205 lncRNAs, 1 out of 26 miRNAs and 8 out of 143 mRNAs were associated with overall survival in Wilms tumor patients (P < 0.05). Conclusions: CeRNA networks played an important role in Wilms tumor. This might provide effective novel insights for further understanding of the mechanisms underlying Wilms tumor.

Download Full-text

Identifying Complex lncRNA/Pseudogene-miRNA-mRNA Crosstalk in Hormone-Dependent Cancers

10.20944/preprints202109.0337.v1 ◽

2021 ◽

Author(s):

Dulari Jayarathna ◽

Miguel E. Rentería ◽

Emilie Sauret ◽

Jyotsna Batra ◽

Neha S. Gandhi

Keyword(s):

Regulatory Networks ◽

Cancer Survival ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Messenger Rnas ◽

Protein Activity ◽

Cerna Network ◽

Non Coding Rnas

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.

Download Full-text

Tumor Microenvironmental Competitive Endogenous RNA Network and Immune Cells Act as Robust Prognostic Predictor of Acute Myeloid Leukemia

Frontiers in Oncology ◽

10.3389/fonc.2021.584884 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yaqi Cheng ◽

Xiaoran Wang ◽

Peiyan Qi ◽

Chengxiu Liu ◽

Shoubi Wang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Immune Cells ◽

Myeloid Leukemia ◽

Immune Cell ◽

The Cancer Genome Atlas ◽

Cerna Network ◽

New Perspective ◽

Highly Correlated ◽

Competitive Endogenous Rna ◽

Acute Myeloid

Acute myeloid leukemia (AML) is malignant hematologic tumors with frequent recurrence and cause high mortality. Its fate is determined by abnormal intracellular competitive endogenous RNA (ceRNA) network and extracellular tumor microenvironment (TME). This study aims to build a ceRNA network related to AML TME to explore new prognostic and therapeutic targets. The RNA expression data of AML were obtained from The Cancer Genome Atlas (TCGA) database. First, we used the ESTIMATE algorithm to calculate the immune cells and stromal cells infiltration scores in the TME and found that all scores were highly correlated with AML’s prognostic characteristics. Subsequently, differentially expressed mRNAs and lncRNAs between high and low score groups were identified to construct a TME-related ceRNA network. Further, the Cox-lasso survival model was employed to screen out the hub prognostic ceRNA network composed of two mRNAs (EPB41L3, COL2A1), three miRNAs (hsa-mir-26a-5p, hsa-mir-148b-3p, hsa-mir-148a-3p), and two lncRNAs (CYP1B1-AS1, C9orf106), and construct nomograms. Finally, we used CIBERSORT algorithm and Kaplan-Meier survival analysis to identify the prognostic TME immune cells and found that naive B cells, M2-type macrophages, and helper follicular T cells were related to prognosis, and the hub ceRNAs were highly correlated with immune cell infiltration. This study provided a new perspective to elucidate how TME regulates AML process and put forward the new therapy strategies combining targeting tumor cells with disintegrating TME.

Download Full-text

Identifying Complex lncRNA/Pseudogene–miRNA–mRNA Crosstalk in Hormone-Dependent Cancers

Biology ◽

10.3390/biology10101014 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1014

Author(s):

Dulari K. Jayarathna ◽

Miguel E. Rentería ◽

Emilie Sauret ◽

Jyotsna Batra ◽

Neha S. Gandhi

Keyword(s):

Regulatory Networks ◽

Cancer Survival ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Messenger Rnas ◽

Protein Activity ◽

Cerna Network ◽

Non Coding Rnas

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that messenger RNAs and other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long-non-coding RNA-associated ceRNA networks. Here, we identify an extended ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of five hormone-dependent (HD) cancers, i.e., prostate, breast, colon, rectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across five HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene-associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding the shared molecular pathogenesis in a group of related diseases.

Download Full-text

Transcriptional factor regulation network and competitive endogenous RNA (ceRNA) network determining response of esophageal squamous cell carcinomas to neoadjuvant chemoradiotherapy

PeerJ ◽

10.7717/peerj.6668 ◽

2019 ◽

Vol 7 ◽

pp. e6668 ◽

Cited By ~ 1

Author(s):

Mingrui Shao ◽

Wenya Li

Keyword(s):

Signaling Pathway ◽

Regulatory Network ◽

Neoadjuvant Chemoradiotherapy ◽

Wnt Signaling Pathway ◽

Squamous Cell Carcinomas ◽

Transcriptional Factor ◽

Cerna Network ◽

Regulation Network ◽

Esophageal Squamous Cell Carcinomas ◽

Competitive Endogenous Rna

Background Neoadjuvant chemoradiotherapy (nCRT) followed by surgery benefits survival for patients with esophageal squamous cell carcinomas (ESCC) compared with surgery alone, but the clinical outcomes of nCRT are heterogeneous. This study aimed to elucidate transcriptional factor (TF) regulation network and competitive endogenous RNA (ceRNA) network determining response of ESCC to nCRT. Materials and Methods RNA microarray data of GSE59974 and GSE45670 were analyzed to investigate the significant changes of lincRNAs, miRNAs, mRNAs in responders and non-responders of nCRT in ESCC. Functional and enrichment analyses were conducted by clusterProfiler. The target lincRNAs and mRNAs of miRNAs were predicted by miRWalk. The ceRNA and TF regulatory networks were constructed using Cytoscape. Results Differentially expressed genes between responders and non-responders mainly enriched in biological process including Wnt signaling pathway and regulation of cell development and morphogenesis involved in differentiation. Besides, these genes showed enrichment in molecular function of glycosaminoglycan binding, metalloendopeptidase inhibitor and growth factor activity. KEGG analysis enriched these genes in pathways of neurotrophin signaling pathway, cell adhesion molecules and Wnt signaling pathway. We also constructed ceRNA network and TF network regulating response of ESCC to nCRT. Core regulatory miRNAs were miR-520a, miR-548am, miR-3184, miR-548d, miR-4725, miR-148a, miR-4659a and key regulatory TFs included MBNL1, SLC26A3, BMP4, ZIC1 and ANKRD7. Conclusion We identified significantly altered lincRNAs, miRNAs and mRNAs involved in the nCRT response of ESCC. In addition, the ceRNA regulatory network of lincRNA-miRNA-mRNA and TF regulatory network were constructed, which would elucidate novel molecular mechanisms determining nCRT response of ESCC, thus providing promising clues for clinical therapy.

Download Full-text