Dataset Information

Comprehensive analysis of differentially expressed circRNAs revealed a ceRNA network in pancreatic ductaladenocarcinoma.

ABSTRACT: Introduction:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. However, the molecular mechanisms underlying PDAC are still not completely understood. Circular RNAs (circRNAs) are a unique class of RNA formed by special loop splicing. More and more researchers have paid attention to circRNAs. Material and methods:In this study, we constructed a circRNA-mediated competing endogenous RNA (ceRNA) network in PDAC. Gene ontology (GO) analysis was performed to explore circRNAs' potential roles in PDAC progression. We also constructed an up-stream transcriptional network of circRNAs' parental genes and found that many transcription factors (TFs), such as tumor protein p53 (TP53) and MYC, could regulate their expression. Results:This study, which aimed to identify differentially expressed circRNAs in PDAC, suggested that circRNAs may also act as biomarkers for PDAC. We analyzed two public datasets (GSE69362 and GSE79634) to identify differentially expressed circRNAs in PDAC. Finally, we found that DExH-Box Helicase 9 (DHX9) may be a potential regulator of circRNA formation in PDAC. Genomic loci of four down-regulated circRNAs - hsa_circ_000691, hsa_circ_0049392, hsa_circ_0005203, and hsa_circ_0001626 - contained DHX9 binding sites, suggesting that they may be directly regulated by DHX9. Conclusions:Our study identified differentially expressed circRNAs in PDAC, suggesting that circRNAs may also act as biomarkers for PDAC. Additional investigations of function and up-stream regulation of differentially expressed circRNA in PDAC are still needed.

SUBMITTER: Zhou JZ

PROVIDER: S-EPMC6657245 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Comprehensive analysis of differentially expressed circRNAs revealed a ceRNA network in pancreatic ductaladenocarcinoma.

Zhou Jin-Zhe JZ Hu Mu-Ren MR Diao Hong-Liang HL Wang Qi-Wei QW Huang Qi Q Ge Bu-Jun BJ

Archives of medical science : AMS 20190515 4

<h4>Introduction</h4>Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. However, the molecular mechanisms underlying PDAC are still not completely understood. Circular RNAs (circRNAs) are a unique class of RNA formed by special loop splicing. More and more researchers have paid attention to circRNAs.<h4>Material and methods</h4>In this study, we constructed a circRNA-mediated competing endogenous RNA (ceRNA) network in PDAC. Gene ontology (GO) analysis was performed to ...[more]

PMID: 31360192

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Project description:BackgroundCircular RNA (circRNA), a novel class of non-coding RNA, has a closed-loop structure with important functions in skeletal muscle growth. The purpose of this study was to investigate the role of differentially expressed circRNAs (DEcircRNAs), as well as the DEcircRNA-miRNA-mRNA regulatory network, at different stages of porcine skeletal muscle development. Here, we present a panoramic view of circRNA expression in porcine skeletal muscle from Large White and Mashen pigs at 1, 90, and 180 days of age.ResultsWe identified a total of 5819 circRNAs. DEcircRNA analysis at different stages showed 327 DEcircRNAs present in both breeds. DEcircRNA host genes were concentrated predominately in TGF-β, MAPK, FoxO, and other signaling pathways related to skeletal muscle growth and fat deposition. Further prediction showed that 128 DEcircRNAs could bind to 253 miRNAs, while miRNAs could target 945 mRNAs. The constructed ceRNA network plays a vital role in skeletal muscle growth and development, and fat deposition. Circ_0015885/miR-23b/SESN3 in the ceRNA network attracted our attention. miR-23b and SESN3 were found to participate in skeletal muscle growth regulation, also playing an important role in fat deposition. Using convergent and divergent primer amplification, RNase R digestion, and qRT-PCR, circ_0015885, an exonic circRNA derived from Homer Scaffold Protein 1 (HOMER1), was confirmed to be differentially expressed during skeletal muscle growth. In summary, circ_0015885 may further regulate SESN3 expression by interacting with miR-23b to function in skeletal muscle.ConclusionsThis study not only enriched the circRNA library in pigs, but also laid a solid foundation for the screening of key circRNAs during skeletal muscle growth and intramural fat deposition. In addition, circ_0015885/miR-23b/SESN3, a new network regulating skeletal muscle growth and fat deposition, was identified as important for increasing the growth rate of pigs and improving meat quality.

Project description:Researchers have been exploring the molecular mechanisms underlying the control of periodontal ligament stem cell (PDLSC) osteogenic differentiation. Recently, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) were shown to function as competitive endogenous RNAs (ceRNAs) to regulate the effect of microRNAs (miRNAs) on their target genes during cell differentiation. However, comprehensive identification and integrated analysis of lncRNAs and circRNAs acting as ceRNAs during PDLSC osteogenic differentiation have not been performed.PDLSCs were derived from healthy human periodontal ligament and cultured separately with osteogenic induction and normal media for 7 days. Cultured PDLSCs were positive for STRO-1 and CD146 and negative for CD31 and CD45. Osteo-induced PDLSCs showed increased ALP (alkaline phosphatase) activity and up-regulated expression levels of the osteogenesis-related markers ALP, Runt-related transcription factor 2 and osteocalcin. Then, a total of 960 lncRNAs and 1456 circRNAs were found to be differentially expressed by RNA sequencing. The expression profiles of eight lncRNAs and eight circRNAs were measured with quantitative real-time polymerase chain reaction and were shown to agree with the RNA-seq results. Furthermore, the potential functions of lncRNAs and circRNAs as ceRNAs were predicted based on miRanda and were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. In total, 147 lncRNAs and 1382 circRNAs were predicted to combine with 148 common miRNAs and compete for miRNA binding sites with 744 messenger RNAs. These mRNAs were predicted to significantly participate in osteoblast differentiation, the MAPK pathway, the Wnt pathway and the signaling pathways regulating pluripotency of stem cells. Among them, lncRNAs coded as TCONS_00212979 and TCONS_00212984, as well as circRNA BANP and circRNA ITCH, might interact with miRNA34a and miRNA146a to regulate PDLSC osteogenic differentiation via the MAPK pathway.This study comprehensively identified lncRNAs/circRNAs and first integrated their potential ceRNA function during PDLSC osteogenic differentiation. These findings suggest that specific lncRNAs and circRNAs might function as ceRNAs to promote PDLSC osteogenic differentiation and periodontal regeneration.

Project description:Previous studies have suggested that long non‑coding RNAs (lncRNAs) are closely associated with human diseases, particularly cancer, including cancer of the lung, breast and stomach. A variety of lncRNAs are abnormally expressed in cancer and participate in several pathways including cell proliferation and apoptosis; these elements are closely associated with the development of cancer. The Cancer Genome Atlas (TCGA) is an important cancer database. It consists of clinical data, genomic variation, mRNA, microRNA (miRNA) and lncRNAs expression, methylation and other data for various types of human cancer. In the present study, differential expression of RNA was identified using the edgeR package. A total 1,222 RNA sequencing profiles from patients with breast cancer were downloaded from TCGA. A competing endogenous RNA (ceRNA) network was constructed for breast cancer based on miRcode and miRTarBase. The top 10 lncRNAs were selected using Cox regression analysis. Survival analysis was performed using Kaplan‑Meier analysis. A total of 1,028 breast cancer‑associated lncRNAs and 89 miRNAs (fold change >2; P<0.05) were identified; among these, 93 lncRNAs and 19 miRNAs were included in the ceRNA network. Subsequently, 10 basic lncRNAs were selected and their associations with overall survival were identified. In addition, 5 lncRNAs (ADAM metallopeptidase with thrombospondin type 1 motif 9‑antisense RNA 1, AL513123.1, chromosome 10 open reading frame 126, long intergenic non‑protein coding RNA 536 and Wilms tumor 1 antisense RNA) were identified to be significantly associated with overall survival (P<0.05, log rank test). These results suggested that mRNAs, lncRNAs and miRNAs were involved in pathological mechanisms of breast cancer. The newly‑identified ceRNA network included 93 breast cancer‑specific lncRNAs, 19 miRNAs and 27 mRNAs. The results of the present study highlight the potential of lncRNAs in understanding the development and pathogenesis of breast cancer, and suggest novel concepts and an experimental basis for the identification of prognostic biomarkers and therapeutic targets for breast cancer.

Dataset Information

Comprehensive analysis of differentially expressed circRNAs revealed a ceRNA network in pancreatic ductaladenocarcinoma.

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Comprehensive analysis of differentially expressed circRNAs revealed a ceRNA network in pancreatic ductaladenocarcinoma.

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