Dataset Information

Bioinformatic analysis reveals an exosomal miRNA-mRNA network in colorectal cancer.

ABSTRACT:

Background

Exosomes play important roles in angiogenesis, drug resistance, and metastasis of colorectal cancer (CRC), but the underlying mechanism has seldom been reported. Herein, our study aimed to reveal an exosomal miRNA-mRNA network involved in CRC by performing bioinformatical analysis.

Methods

The mRNA and miRNA data of colon adenocarcinoma and rectal adenocarcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and exosomal miRNAs data were downloaded from the GEO dataset GSE39833. The differential expression analysis was performed using "limma" and "edgeR". Target mRNAs of miRNAs were predicted using FunRich 3.1.3, miRNAtap and multiMiR. The candidate mRNAs and exosomal miRNAs were obtained by intersecting two groups of differentially expressed miRNAs and intersection of the differential expressed mRNAs and the target mRNAs, respectively. Key mRNAs and exosomal miRNAs were identified by the least absolute shrinkage and selection operator regression analysis, and used to construct the exosomal miRNA-mRNA network. The network verified was by receiver operating characteristic curve, GEPIA and LinkedOmics. Functional enrichment analysis was also performed for studied miRNAs and mRNAs.

Results

A total of 6568 differentially expressed mRNAs and 531 differentially expressed miRNAs from TCGA data, and 166 differentially expressed exosomal miRNAs in GSE39833 dataset were identified. Next, 16 key mRNAs and five key exosomal miRNAs were identified from the 5284 candidate mRNAs and 61 candidate exosomal miRNAs, respectively. The exosomal miRNA-mRNA network with high connectivity contained 13 hub mRNAs (CBFB, CDH3, ETV4, FOXQ1, FUT1, GCNT2, GRIN2D, KIAA1549, KRT80, LZTS1, SLC39A10, SPTBN2, and ZSWIM4) and five hub exosomal miRNAs (hsa-miR-126, hsa-miR-139, hsa-miR-141, hsa-miR-29c, and hsa-miR-423). The functional annotation revealed that these hub mRNAs were mainly involved in the regulation of B cell receptor signaling pathway and glycosphingolipid biosynthesis related pathways. All hub mRNAs and hub exosomal miRNAs exhibited high diagnosis value for CRC. Furthermore, the association of the hub mRNAs with overall survival, stages, and MSI phenotype of CRC revealed their important roles in CRC progression.

Conclusion

This study constructed an exosomal miRNA-mRNA network which may play crucial roles in the carcinogenesis and progression of CRC, thus providing potential diagnostic biomarkers and therapeutic targets for CRC.

SUBMITTER: Ma J

PROVIDER: S-EPMC7913431 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bioinformatic analysis reveals an exosomal miRNA-mRNA network in colorectal cancer.

Ma Jun J Wang Peilong P Huang Lei L Qiao Jianxia J Li Jianhong J

BMC medical genomics 20210227 1

<h4>Background</h4>Exosomes play important roles in angiogenesis, drug resistance, and metastasis of colorectal cancer (CRC), but the underlying mechanism has seldom been reported. Herein, our study aimed to reveal an exosomal miRNA-mRNA network involved in CRC by performing bioinformatical analysis.<h4>Methods</h4>The mRNA and miRNA data of colon adenocarcinoma and rectal adenocarcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and exosomal miRNAs data were downloaded from t ...[more]

PMID: 33639954

Similar Datasets

Project description:BACKGROUND:Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been found to act as microRNA (miRNA) sponges and thus play key roles in biological processes and pathogenesis. However, studies regarding circRNAs in colorectal cancer (CRC) remain inadequate. RESULTS:By differential expression analysis, 10 candidate circRNAs (6 upregulated and 4 downregulated circRNAs) were chosen. 9 of 10 circRNAs were available on CSCD and their structure showed the binding potential of miRNA. Intersection analysis revealed that miR-145-5p, miR-3127-5p, miR-761, miR-4766-3p, miR-135a-5p, miR-135b-5p, miR-374a-3p and miR-330-3p were 8 miRNAs with the most potential in binding circRNAs. Further expression validation and correlation analysis demonstrated hsa_circ_0001955/miR-145-5p and hsa_circ_0000977/miR-135b-5p axes as key pathways in CRC. Subsequently, target gene prediction, differential expression analysis, intersection analysis and correlation analysis showed that CDK6, MMP12 and RAB3IP were the three potential downstream targets of hsa_circ_0001955/miR-145-5p axis and FOXO1, MBNL1, MEF2C, RECK, PPM1E, TTLL7 and PCP4L1 were the seven potential downstream targets of hsa_circ_0000977/miR-135b-5p axis in CRC. Finally, we also confirmed that expression of hsa_circ_0001955 or hsa_circ_0000977 was significantly positively correlated with their individual targets in CRC. CONCLUSIONS:In the present work, we constructed a potential hsa_circ_0001955/hsa_circ_0000977-mediated circRNA-miRNA-mRNA regulatory network in CRC by a series of in silico analysis and experimental validation. METHODS:Whole-transcriptome microarrays from CRC and matched normal samples were obtained from GEO. The structure of circRNA was identified by CSCD. starBase and miRNet were successively used to predict miRNA of circRNA and target gene of miRNA. Expression correlation between RNA-RNA interactions was assessed using GEO and TCGA data. Finally, a potential circRNA-miRNA-mRNA network was established based on competing endogenous RNA (ceRNA) hypothesis.

Project description:BackgroundThe adrenal gland participates in the process of sheep reproduction. MicroRNAs (miRNAs), endogenous small noncoding RNAs, regulate gene expression at the posttranscriptional level. However, the miRNA-mRNA network profile of adrenal glands relating to reproduction in sheep is still not well-studied. As sheep with FecBBB genotype show higher lambing number compare with the sheep with FecB++ genotype. This research aims to compare gene expression by small RNA-seq in adrenal tissues at follicular (F) and luteal (L) phases in FecBBB (MM) and FecB++ (ww) sheep. After analysis of gene expression, significant differentially expressed microRNAs (DEMs) and corresponding target genes were identified.ResultsA total of 180 miRNAs were found in this study, of which 19 DEMs were expressed in the four comparison groups (MM_F_A vs. MM_L_A, MM_F_A vs. ww_F_A, MM_L_A vs. ww_L_A, ww_F_A vs. ww_L_A). Subsequently, 354 target genes of 19 DEMs were predicted by integrated analysis. Cluster analysis was performed by K_means_cluster, and the expression patterns of these DEMs were separated into four subclusters. Functional analysis of target genes was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The results indicated that the target genes were involved mainly in the Notch signaling pathway, signal transduction, cell communication, innate immune response and amino acid metabolism. Specifically, the Notch signaling pathway, biosynthetic process and metabolic process of pyrimidine nucleotide and amino acid metabolism appear to play key regulatory roles in the sheep fertility trait. Furthermore, miRNA-mRNA interaction networks were constructed by differentially expressed genes combined with our previous study of transcriptome data. The results showed that several key genes, including TDRD3, ANAPC7, CCNL2, BRD2 and MUT, were related to the transformation from the follicular phase to the luteal phase. PLAC8L1, NFAT5, DDX24 and MBD1 were related to the high fecundity of small tail Han sheep.ConclusionsIn this study, the miRNA transcriptome profile was identified, and miRNA-mRNA interaction networks were constructed in adrenal gland tissue of small tail Han sheep, the interaction between miR-370-3p and its targets were considered to play a major role in the reproduction regulation process. The results enriched the number of known miRNAs in adrenal glands and provided novel ideas and further information to demonstrate posttranscriptional regulation mechanisms at follicular and luteal phases in different genotypes of small tail Han sheep.

Project description:BackgroundAccumulating evidence supports the importance of noncoding RNAs and exosomes in coronary heart disease (CHD). However, exosomal-associated competing endogenous RNA- (ceRNA-) mediated regulatory mechanisms in CHD are largely unexplored. The present study aimed to explore exosomal-associated ceRNA networks in CHD.MethodsData from 6 CHD patients and 32 normal controls were downloaded from the ExoRBase database. CHD and normal controls were compared by screening differentially expressed mRNAs (DEMs), lncRNAs (DELs), and circRNAs (DECs) in serum exosomes. MicroRNAs (miRNAs) targeting DEMs were predicted using the Targetscan and miRanda databases, and miRNAs targeted by DELs and DECs were predicted using the miRcode and starBase databases, respectively. The biological functions and related signaling pathways of DEMs were analyzed using the David and KOBAS databases. Subsequently, a protein-protein interaction (PPI) network was established to screen out on which hub genes enrichment analyses should be performed, and a ceRNA network (lncRNA/circRNA-miRNA-mRNA) was constructed to elucidate ceRNA axes in CHD.ResultsA total of 312 DEMs, 43 DELs, and 85 DECs were identified between CHD patients and normal controls. Functional enrichment analysis showed that DEMs were significantly enriched in "chromatin silencing at rDNA," "telomere organization," and "negative regulation of gene expression, epigenetic." PPI network analysis showed that 25 hub DEMs were closely related to CHD, of which ubiquitin C (UBC) was the most important. Hub genes were mainly enriched in "cellular protein metabolic process" functions. The exosomal-associated ceRNA regulatory network incorporated 48 DEMs, 73 predicted miRNAs, 10 DELs, and 15 DECs. The LncRNA/circRNA-miRNA-mRNA interaction axes (RPL7AP11/hsa-miR-17-5p/UBC and RPL7AP11/hsa-miR-20b-5p/UBC) were obtained from the network.ConclusionsOur findings provide a novel perspective on the potential role of exosomal-associated ceRNA network regulation of the pathogenesis of CHD.

Project description:BackgroundThe high morbidity and mortality of colorectal cancer (CRC) have posed great threats to human health. Circular RNA (CircRNA) and microRNA (miRNA), acting as competing endogenous RNAs (ceRNAs), have been found to play vital roles in carcinogenesis. However, the biological function of ceRNAs in CRC pathogenesis and prognosis remains largely unexplored.AimTo identify the CRC-specific circRNA-miRNA-mRNA regulatory network and uncover the subnetwork associated with its prognosis.MethodsCircRNAs, miRNAs and mRNAs differentially expressed (DE) in CRC tissues were selected by expression file analysis in the Gene Expression Omnibus (GEO) database, and the downstream target molecules of circRNAs and miRNAs were predicted. Then, the intersection of differentially expressed RNA molecules with the predicted targets was determined to obtain a ceRNA network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the possible mechanism of pathogenesis. A survival analysis using the gene profiles and clinical information in The Cancer Genome Atlas (TCGA) database was performed to identify the mRNAs associated with the clinical outcome of CRC patients and construct a prognostic subnetwork.ResultsWe downloaded three datasets (GSE126095, GSE41655 and GSE41657) of large-scale CRC samples from the GEO database. There were 55 DEcircRNAs, 114 DEmiRNAs and 267 DEmRNAs in CRC tissues compared with normal tissues. After intersecting these molecules with predicted targets, 19 circRNAs, 13 miRNAs and 28 mRNAs were chosen to develop a circRNA-miRNA-mRNA network. GO and KEGG functional enrichment analyses indicated that the retinol metabolic process, leukocyte chemotaxis, extracellular matrix remodeling, endoplasmic reticulum stress, alcohol dehydrogenase activity, gastric acid secretion, nitrogen metabolism and NOD-like receptor signaling pathway might participate in the tumorigenesis of CRC. After verifying the identified mRNA effect in the TCGA database, we finally recognized 3 mRNAs (CA2, ITLN1 and LRRC19) that were significantly associated with the overall survival of CRC patients and constructed a ceRNA subnetwork including 5 circRNAs (hsa_circ_0080210, hsa_circ_0007158, hsa_circ_0000375, hsa_circ_0018909 and hsa_circ_0011536) and 3 miRNAs (hsa-miR-601, hsa-miR-671-5p and hsa-miR-765), which could contain innovative and noninvasive indicators for the early screening and prognostic prediction of CRC.ConclusionWe proposed a circRNA-miRNA-mRNA regulatory network closely associated with the progression and clinical outcome of CRC that might include promising biomarkers for carcinogenesis and therapeutic targets.

Dataset Information

Bioinformatic analysis reveals an exosomal miRNA-mRNA network in colorectal cancer.

Background

Methods

Results

Conclusion

Publications

Bioinformatic analysis reveals an exosomal miRNA-mRNA network in colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets