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Extended transcriptome analysis reveals genome-wide lncRNA-mediated epigenetic dysregulation in colorectal cancer.

ABSTRACT: It is estimated that the rate of epigenetic changes may be orders of magnitude higher than that of genetic changes and that purely epigenetic mechanisms may explain why cancers arise with few or no recurrent mutations. However, supporting evidence remains limited, partly due to the cost of experimentally studying genome-wide epigenetic dysregulation. Since genome modification enzymes are recruited by long noncoding RNAs (lncRNAs) to specific genomic sites, analyzing differentially expressed genes and differentially methylated regions (DMRs) at the DNA binding sites of differentially expressed lncRNAs is important for uncovering epigenetic dysregulation. We performed RNA-seq and MeDIP-seq on a set of colorectal cancer (CRC) and normal colon samples and developed an analysis pipeline for combined analyses of gene expression, DNA methylation, and lncRNA/DNA binding. The genes identified in our data and important for CRC agree with widely reported findings. We found that aberrantly transcribed noncoding transcripts may epigenetically dysregulate genes, that correlated gene expression is significantly determined by epigenetic dysregulation, that differentially expressed noncoding transcripts and their epigenetic targets form distinct modules in different cancer cells, and that many hub lncRNAs in these modules are primate-specific. These results suggest that lncRNA-mediated epigenetic dysregulation greatly determines aberrant gene expression and that epigenetic dysregulation is highly species-specific. The analysis pipeline can effectively unveil cancer- and cell-specific modules of epigenetic dysregulation, and such modules may provide novel clues for identifying diagnostic, therapeutic, and prognostic targets for epigenetic dysregulation.

SUBMITTER: He S

PROVIDER: S-EPMC7695927 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Extended transcriptome analysis reveals genome-wide lncRNA-mediated epigenetic dysregulation in colorectal cancer.

He Sha S Chen Juanzhi J Gao Huan H Yang Guixian G Zhang Feixiang F Ding Yanqing Y Zhu Hao H

Computational and structural biotechnology journal 20201114

It is estimated that the rate of epigenetic changes may be orders of magnitude higher than that of genetic changes and that purely epigenetic mechanisms may explain why cancers arise with few or no recurrent mutations. However, supporting evidence remains limited, partly due to the cost of experimentally studying genome-wide epigenetic dysregulation. Since genome modification enzymes are recruited by long noncoding RNAs (lncRNAs) to specific genomic sites, analyzing differentially expressed gene ...[more]

PMID: 33304451

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Project description:Genetic resistance to blackleg (Leptosphaeria maculans, Lm) of canola (Brassica napus, Bn) has been extensively studied, but the mechanisms underlying the host-pathogen interaction are still not well understood. Here, a comparative transcriptome analysis was performed on a resistant doubled haploid Bn line carrying the resistance gene Rlm1 following inoculation with a virulent (avrLm1) or avirulent (AvrLm1) Lm isolate on cotyledons. A total of 6999 and 3015 differentially expressed genes (DEGs) were identified, respectively, in inoculated local tissues with compatible (susceptible) and incompatible (resistant) interactions. Functional enrichment analysis found several biological processes, including protein targeting to membrane, ribosome and negative regulation of programmed cell death, were over-represented exclusively among up-regulated DEGs in the resistant reaction, whereas significant enrichment of salicylic acid (SA) and jasmonic acid (JA) pathways observed for down-regulated DEGs occurred only in the susceptible reaction. A heat-map analysis showed that both biosynthesis and signaling of SA and JA were induced more significantly in the resistant reaction, implying that a threshold level of SA and JA signaling is required for the activation of Rlm1-mediated resistance. Co-expression network analysis revealed close correlation of a gene module with the resistance, involving DEGs regulating pathogen-associated molecular pattern recognition, JA signaling and transcriptional reprogramming. Substantially fewer DEGs were identified in mock-inoculated (control) cotyledons, relative to those in inoculated local tissues, including those involved in SA pathways potentially contributing to systemic acquired resistance (SAR). Pre-inoculation of cotyledon with either an avirulent or virulent Lm isolate, however, failed to induce SAR on remote tissues of same plant despite elevated SA and PR1 protein. This study provides insights into the molecular mechanism of Rlm1-mediated resistance to blackleg.

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Dataset Information

Extended transcriptome analysis reveals genome-wide lncRNA-mediated epigenetic dysregulation in colorectal cancer.

Publications

Extended transcriptome analysis reveals genome-wide lncRNA-mediated epigenetic dysregulation in colorectal cancer.

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