Abstract
Long non-coding RNA (lncRNA) has been confirmed to act as a key regulatory molecule in different types of cancers and play a significant role in tumors initiation and progression. LncRNA can be as acompeting endogenous RNA(ceRNA) to regulate the expression of targeted genes by sponging miRNA. In the present study, we explore the functional roles and regulatory mechanisms of lncRNAs as ceRNAs in colon cancer and their potential implications for prognosis.The lncRNAs, miRNAs and mRNAs expression profiles of 341 colon cancer tissues and 27 non-tumor colon tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Differential expression of RNAs was identified using the “DESeq” bioconductor package in R. PPI network of differentially expressed genes was constructed using the STRING database. Survival analysis was estimated based on Kaplan-Meier curve analysis. We used KOBAS 3.0 to analyze the KEGG pathway of DEGs. The dysregulated lncRNA-associated ceRNA network was constructed in colon cancer based on bioinformatics generated from miRanda, PicTar, TargetScan, miRDB and miRcode. A total of 791 DElncRNAs and 200 DEmiRNAs were identified in colon cancer compared with matched normal tissues with thresholds of |log2foldChange (FC)| >3.0and adjusted P value<0.05.Twenty DElncRNAs were identified, may be related to tumorigenesis and/or progression of colon cancer. Nine out of 20 dysregulated lncRNA were found to be significantly associated with overall survival (P value<0.05). Finally, we successfully constructed colon cancer-associated ceRNA network, including 9 colon cancer-specific lncRNAs, 13 miRNAS and 70 mRNAs. In conclusion, our study will contribute to improve the understanding of ceRNA network regulatory mechanisms in colon cancer. These identified novel lncRNAs can be as candidate prognostic biomarkers or potential therapeutic targets.
Highlights
Colon cancer is one of the most prevalent malignancies in the world and it’s the third leading causes of mortality worldwide[1]
We found that 9 of 12 DElncRNAs were considered as key DElncRNAs responsible for the prognosis of colon cancer
Research reported that up-regulation of Long non-coding RNA (lncRNA) H19 significantly promotes epithelial to mesenchymal transition (EMT) progression and accelerates colorectal cancer cell growth by competing binding the miR-138 and miR-200a to modulate the derepression of targeted genes Vimentin, ZEB1, and ZEB2[24]
Summary
A total of 341 colon cancer cases were enrolled for comprehensively integrated analysis. The colon cancer level 3 RNAseq and miRNASeq of 341 colon cancer samples and corresponding clinical data (S1 File) were downloaded from TCGA database using the Data Transfer Tool (provided by GDC Apps)(https://tcga-data.nci.nih.gov/). The RNAseq and survival data were anonymised before we accessed them. These data were included 341 colon cancer samples and 27 non-cancer samples. That sequence data was derived from Illumina HiSeqRNASeq and Illumina HiSeqmiRNASeq platforms. Our research meets publication guidelines provided by TCGA (http://cancergenome.nih.gov/publications/publicationguidelines)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
