Abstract
Over the past few decades, researchers have become aware of the importance of non-coding RNA, which makes up the vast majority of the transcriptome. Long non-coding RNAs (lncRNAs) in turn constitute the largest fraction of non-coding transcripts. Increasing evidence has been found for the crucial roles of lncRNAs in both tissue homeostasis and development, and for their functional contributions to and regulation of the development and progression of various human diseases such as cancers. However, so far, only few findings with regards to functional lncRNAs in cancers have been translated into clinical applications. Based on multiple factors such as binding affinity of miRNAs to their lncRNA sponges, we analyzed the competitive endogenous RNA (ceRNA) network for the colorectal cancer RNA-seq datasets from The Cancer Genome Atlas (TCGA). After performing the ceRNA network construction and survival analysis, the lncRNA KCNQ1OT1 was found to be significantly upregulated in colorectal cancer tissues and associated with the survival of patients. A KCNQ1OT1-related lncRNA-miRNA-mRNA ceRNA network was constructed. A gene set variation analysis (GSVA) indicated that the expression of the KCNQ1OT1 ceRNA network in colorectal cancer tissues and normal tissues were significantly different, not only in the TCGA-COAD dataset but also in three other GEO datasets used as validation. By predicting comprehensive immune cell subsets from gene expression data, in samples grouped by differential expression levels of the KCNQ1OT1 ceRNA network in a cohort of patients, we found that CD4+, CD8+, and cytotoxic T cells and 14 other immune cell subsets were at different levels in the high- and low-KCNQ1OT1 ceRNA network score groups. These results indicated that the KCNQ1OT1 ceRNA network could be involved in the regulation of the tumor microenvironment, which would provide the rationale to further exploit KCNQ1OT1 as a possible functional contributor to and therapeutic target for colorectal cancer.
Highlights
Colorectal cancer (CRC) is a common malignant cancer and is the second-highest contributor to the worldwide incidence of cancer-related deaths (Miller et al, 2019)
We investigated the KCNQ1OT1 by mining the CRC RNA-Seq dataset in The Cancer Genome Atlas (TCGA), tested its prognostic potential in a CRC cohort and constructed the KCNQ1OT1-related Long non-coding RNAs (lncRNAs)-miRNA-mRNA competitive endogenous RNA (ceRNA) network
After TMM normalization and voom transformation, we explored the DGEs based on GLM likelihood ratio test, 2935 CRC tissue-specific mRNAs and 213 lncRNAs via the differential expression analysis of the TCGA-COAD dataset (Supplementary Figures S1A,B, Supplementary Table S2)
Summary
Colorectal cancer (CRC) is a common malignant cancer and is the second-highest contributor to the worldwide incidence of cancer-related deaths (Miller et al, 2019). CRC develops sporadically from some inflammatory bowel diseases or hereditary cancer syndromes. The development of colorectal cancer is based on the adenoma-carcinoma sequence. The molecular mechanism of the adenoma-carcinoma sequence has been only partly identified. CRC prognosis depends on factors ceRNA Network in Colorectal Cancer related to the patient and treatment. The expertise of the treatment team is one of the most important determinants of the outcome. Detection of CRC cells and cancer precursor cells significantly reduce morbidity and improve patient prognosis (Sung et al, 2021)
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