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TableNONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block

ABSTRACT: Objective: We intended to explore the potential molecular mechanisms underlying cardiac conduction block inducted by UT-B deletion at the transcriptome level. Methods: The heart tissues were harvested from UT-B null mice and age-matched wild-type mice for lncRNA sequencing analysis. Based on the sequencing data, the differentially expressed mRNAs (DEMs) and lncRNAs (DELs) between UT-B knockout and control groups were identified, followed by function analysis and mRNA-lncRNA co-expression analysis. The miRNAs were predicted, and then the competing endogenous RNA (ceRNA) network was constructed. Results: UT-B deletion results in the aberrant expression of 588 lncRNAs and 194 mRNAs. These DEMs were significantly enriched in inflammation-related pathway. A lncRNA-mRNA co-expression network and a ceRNA network was constructed on the basis of the DEMs and DELs. C7 (complement C7)-NONMMUT137216.1 co-expression pair had the highest correlation coefficient in the co-expression network. NONMMUT140591.1 had the highest degree in ceRNA network and involved in ceRNA of NONMMUT140591.1-mmu-miR-298-5p-Gata5 (GATA binding protein 5). Conclusion: UT-B deletion may promote cardiac conduction block via inflammatory process. The ceRNA NONMMUT140591.1-mmu-miR-298-5p-Gata5 may be a potential molecular mechanism of UT-B knockout-induced cardiac conduction block.

ORGANISM(S): Mus musculus

PROVIDER: GSE168717 | GEO | 2021/03/12

REPOSITORIES: GEO

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Project description:5-Fluorouracil (5-FU) is one of the most effective and widely used chemotherapeutic drugs in the treatment of colon cancer. Yet chemoresistance is a common feature of colon cancer, resulting in poor prognosis and short survival. Dynamic reprogramming of chromatin accessibility allows rapid access of the gene regulatory machinery to open genomic regions facilitating subsequent gene expression via direct transcription factor activation and regulatory element-binding. To better understand the regulatory network underlying 5-FU resistance in colon cancer cells, we explored the systematic alterations of chromatin accessibility and transcript expression by the assay for transposase-accessible chromatin using sequencing (ATAC-seq) in combination with transcriptome sequencing, followed by integrative analysis to identify potential regulators and their targets associated with differentially accessible regions (DARs) in 5-FU-resistant HCT15 (HCT15-FR) cells. A total of 3175 differentially expressed mRNAs (DEGs), lncRNAs (DELs) and miRNAs (DEMs) related to 5-FU resistance were identified, including dramatically up-regulated IL33, H19, miR-17-5p, significantly down-regulated AKR1B10, LINC01012, miR-125b-5p, and potential chromatin modifiers such as INO80C, HDAC6 and KDM5A. A competitive endogenous RNAs (ceRNAs) regulatory network was established based on information about interactions among DEGs, DELs and DEMs, suggesting that H19, HOXA11-AS and NEAT1 might function as ceRNAs associate with 5-FU resistance in HCT15 cells. By integrating with transcriptome data, 9868 DARs were identified in HCT15-FR cells compared to control, which were positively (r = 0.58) correlated with their nearest DEGs and DELs. The up-regulated genes related to 4937 increased chromatin-accessible regions were significantly enriched in signaling pathways of MAPK, FOX and WNT, while the 4931 decreased chromatin-accessible regions were considered to be involved in declined biosynthesis of amino acids and nucleotide sugars, signaling pathways of Notch, and HIF-1. Analyses of the DAR sequences revealed that, besides AP-1 family, the TF DNA-binding motifs of FOX and KLF family members were highly enriched in hyper- and hypo-accessible regions, respectively. Moreover, relationships of critical TFs and their potential targets associated with DARs were identified, such as FOXA1, RUNX2, KLF3 and GRHL2. These data provided clear insights and valuable resources for an improved understanding of the non-genetic landscape of 5-FU-resistant colon cancer cells based on chromatin accessibility and transcript levels, which allowed for genome-wide detection of TF-binding sites, potential cis-regulatory elements and therapeutic targets.

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TableNONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block

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