Dataset Information

Contributions of Gene Modules Regulated by Essential Noncoding RNA in Colon Adenocarcinoma Progression.

ABSTRACT: Noncoding RNAs (ncRNAs), especially microRNA (miRNA) and long noncoding RNA (lncRNA), have an impact on a variety of important biological processes during colon adenocarcinoma (COAD) progression. This includes chromatin organization, transcriptional and posttranscriptional regulation, and cell-cell signaling. The aim of this study is to identify the ncRNA-regulated modules that accompany the progression of COAD and to analyze their mechanisms, in order to screen the potential prognostic biomarkers for COAD. An integrative molecular analysis was carried out to identify the crosstalks of gene modules between different COAD stages, as well as the essential ncRNAs in the posttranscriptional regulation of these modules. 31 ncRNA regulatory modules were found to be significantly associated with overall survival in COAD patients. 17 out of the 31 modules (in which ncRNAs played essential roles) had improved the predictive ability for COAD patient survival compared to only the mRNAs of those modules, which were enriched in the core cancer hallmark pathways with closer interactions. These suggest that the ncRNAs' regulatory modules not only exhibit close relation to COAD progression but also reflect the dynamic significant crosstalk of genes in the modules to the different malignant extent of COAD.

SUBMITTER: Li C

PROVIDER: S-EPMC7128050 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Contributions of Gene Modules Regulated by Essential Noncoding RNA in Colon Adenocarcinoma Progression.

Li Chunhua C Yu Xiaorong X Lu Jianping J Zheng Liyu L Xu Dahua D Xu Zelong Z Wang Liqiang L Cui Ying Y Li Yeshuang Y Wang Hong H Xu Jiankai J Li Kongning K

BioMed research international 20200320

Noncoding RNAs (ncRNAs), especially microRNA (miRNA) and long noncoding RNA (lncRNA), have an impact on a variety of important biological processes during colon adenocarcinoma (COAD) progression. This includes chromatin organization, transcriptional and posttranscriptional regulation, and cell-cell signaling. The aim of this study is to identify the ncRNA-regulated modules that accompany the progression of COAD and to analyze their mechanisms, in order to screen the potential prognostic biomarke ...[more]

PMID: 32280704

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Project description:Background: Long noncoding RNAs (lncRNAs) crucially modulate DNA damage responses/repair in cancer cells. However, the underlying regulatory role of genome integrity and its clinical value in colon adenocarcinoma (COAD) remains unclear. This study links genome instability to lncRNA using computational biology techniques, in attempt to propose novel biomarkers of immunotherapy outcome, and investigated a potential competing endogenous RNA (ceRNA) as a molecular regulatory mechanism. Methods: TCGA-COAD patients were divided into genome unstable (GU)-like and genome stable (GS)-like clusters via hierarchical clustering to predict immunotherapy outcomes. Multivariate Cox model was established to predict the overall survival rate in COAD patients. Additionally, SVM and LASSO algorithms were applied to obtain hub lncRNAs. A novel genome instability-related ceRNA network was predicted with the Starbase 2.0 database. To better understand how these genes fundamentally interact during tumor progression and development, the mutation analysis and single-gene analysis for each gene was performed. Results: In contrast to those in the GS-like cluster, GU-like-cluster patients demonstrated a higher tumor mutational burden (TMB)/microsatellite instability (MSI), DNA polymerase epsilon (POLE) mutation rate, and immune checkpoint expression, all indicate a greater predictive power for response rate for immunotherapy. The novel prognostic signature demonstrated an outstanding predictive performance (AUC > 0.70). The genes in the genome insatiability-related ceRNA network (including four axes: AL161772.1-has-miR-671-5p (hsa-miR-181d-5p, has-miR-106a-5p)-NINL, AL161772.1-has-miR-106a-5p-TNFSF11, AC124067.4-hsa-miR-92b-3p (hsa-miR-589-5p)-PHYHIPL, and BOLA3-AS1-has-miR-130b-3p-SALL4) were identified as critical regulators of tumor microenvironment infiltration, cancer stemness, and drug resistance. qPCR was performed to validate the expression patterns of these genes. Furthermore, the MSI-high proportion was greater in patients with mutated type than in those with the wild type according to all four target genes, indicating that these four genes modulate genomic integrity and could serve as novel immunotherapy biomarkers. Conclusion: We demonstrated that genome instability-related lncRNA is a novel biomarker for immunotherapy outcomes and prognosis. A novel ceRNA network that modulates genomic integrity, including four lncRNA-miRNA-mRNA axes, was proposed.

Dataset Information

Contributions of Gene Modules Regulated by Essential Noncoding RNA in Colon Adenocarcinoma Progression.

Publications

Contributions of Gene Modules Regulated by Essential Noncoding RNA in Colon Adenocarcinoma Progression.

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