Investigation of MicroRNA and transcription factor mediated regulatory network for silicosis using systems biology approach

Abstract

Silicosis is a major health issue among workers exposed to crystalline silica. Genetic susceptibility has been implicated in silicosis. The present research demonstrates key regulatory targets and propagated network of gene/miRNA/transcription factor (TF) with interactions responsible for silicosis by integrating publicly available microarray data using a systems biology approach. Array quality is assessed with the Quality Metrics package of Bioconductor, limma package, and the network is constructed using Cytoscape. We observed and enlist 235 differentially expressed genes (DEGs) having up-regulation expression (85 nos) and down-regulation expression (150 nos.) in silicosis; and 24 TFs for the regulation of these DEGs entangled with thousands of miRNAs. Functional enrichment analysis of the DEGs enlighten that, the maximum number of DEGs are responsible for biological process viz, Rab proteins signal transduction (11 nos.) and Cellular Senescence (20 nos.), whereas IL-17 signaling pathway (16 nos.) and Signalling by Nuclear Receptors (14 nos.) etc. are Biological Pathway involving more DEGs. From the identified 1100 high target microRNA (miRNA)s involved in silicosis, 1055 miRNAs are found to relate with down-regulated genes and 847 miRNAs with up-regulated genes. The CDK19 gene (Up-regulated) is associated with 617 miRNAs whereas down-regulated gene ARID5B is regulated by as high as 747 high target miRNAs. In Prediction of Small-molecule signatures, maximum scoring small-molecule combinations for the DEGs have shown that CGP-60774 (with 20 combinations), alvocidib (with 15 combinations) and with AZD-7762 (24 combinations) with few other drugs having the high probability of success.

Identification of the shared gene signatures and pathways between polycystic ovary syndrome and endometrial cancer: An omics data based combined approach

“…TFs control gene expression by directly binding to DNA sequences of target genes thus play a regulatory role in transcription and translation processes [ 35 , 36 ]. Moreover, miRNAs modulate mRNA translation and transcript degradation [ 37 ]. TFs and miRNAs modulate genetic expressions which may result in formation of cancer cells [ 38 ].…”

Using publicly available datasets to identify population-based transcriptomic landscape contributing to the aggressiveness of breast cancer in young women

“…C17ORF58 (Chromosome 17 Open Reading Frame 58) chr17p13.1 Reported to up-regulate CENPF gene, which is associated with bone metastasis by the activation of the PI3K-AKT pathway (Sun et al, 2019;Choudhari et al, 2021) ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1) chr17q23.3 Understudied kinase, codes for IRE1β, which is an unfolded protein that is part of a cancer pathway hijacked by cancer cells (Essegian et al, 2020) PSMD12 (Proteasome 26S Subunit, Non-ATPase 12) crh17q24.2 Promotes cell proliferation and metastasis and inhibits pro-apoptotic genes (Du et al, 2020) FREM2 (FRAS1 Related Extracellular Matrix 2) chr13q13.3 Overexpression correlates with poor outcomes in glioma patients (Zolotovskaia et al, 2021) LINC00332 chr12q13.3 Highest expression in testis (from GTEx RNA-seq of 17,382 samples).…”

Silica-associated lung disease in developing countries

“…Developing countries having the highest burden of this disease are ideally suited for such research and clinical trials. Recently, in a study from India, 235 differentially expressed genes having upregulated or downregulated expression were analysed in silicosis along with the associated transcription factors and micro RNAs [108]. Through predictive modelling, the compounds CGP-60774, alvocidib and AZD-7762 were found to have a high probability of success.…”