Integrated Analysis of lncRNA and mRNA Transcriptomes Reveals New Regulators of Ubiquitination and the Immune Response in Silica-Induced Pulmonary Fibrosis

Abstract

Objectives As an epigenetic player, long noncoding RNAs (LncRNAs) have been reported to participate in multiple biological processes; however, their biological functions in silica-induced pulmonary fibrosis (SIPF) occurrence and development remain incompletely understood. Methods Five case/control pairs were used to perform integrated transcriptomes analysis of lncRNA and mRNA. Prediction of lncRNA and mRNA functions was aided by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Additionally, we constructed a coexpression network of lncRNAs and mRNAs to identify targets of regulation. Results In total, 1069 differentially expressed mRNAs and 366 lncRNAs were identified with the changes more than 2 times (p<0.05), of which 351 downregulated mRNA and 31 downregulated lncRNA were <0.5 (p<0.05) and those of 718 upregulated mRNAs and 335 upregulated lncRNA were >2 (p<0.05). The levels of 10 lncRNAs were measured via qRT-PCR; the results were consistent with the microarray data. Four genes named of FEM1B, TRIM39, TRIM32, and KLHL15 were enriched significantly with ubiquitination and immune response. Cytokine-cytokine receptor interaction was the most significantly enriched KEGG pathway in both mRNAs and lncRNAs. The coexpression network revealed that a single lncRNA can interact with multiple mRNAs, and vice versa. Conclusions lncRNA and mRNA expression were aberrant in patients with SIPF compared to controls, indicating that differentially expressed lncRNAs and mRNAs may play critical roles in SIPF development. Our study affords new insights into the molecular mechanisms of SIPF and identifies potential biomarkers and targets for SIPF diagnosis and treatment.

PRKCSH Alternative Splicing Involves in Silica-Induced Expression of Epithelial–Mesenchymal Transition Markers and Cell Proliferation

“…However, extensive further work is needed to identify the functional consequences of AS events in the condition of certain stress stimulation. Here, based on our laboratory studies on the transcriptomics of silica-induced lung fibrosis previously, 11 we noted an increased AS events in the silica-induced lung fibrosis. Bioinformatic analysis and characterization of these AS events uncovered some genes involved in significant AS events.…”

“…Details of the baseline information including the inclusion criteria, environmental silica concentration exposure, mean weight, and the blood sample storage condition are presented in our previous study. 11 The study was performed in accordance with all relevant tenets of the Declaration of Helsinki and was approved by the Ethics Committee of Xiangya School of Public Health (Approval no. XYGW-2018-11).…”

“…Our previous published reports have demonstrated that over the past several decades, more than 60 000 silicosis have been recorded and the new silicosis cases gradually increased each year with reported approximately 24,000 deaths annually. 10,11 Due to no effective treatments for silicosis available currently, needs to highlight the insights of molecular mechanisms in diagnoses and treatment of this disease are very urgent. 5,12…”

Integrated analysis of transcriptomic and metabolomic profiling reveal the p53 associated pathways underlying the response to ionizing radiation in HBE cells

“…qRT-PCR was carried out in our laboratory using the Super Real PreMix Plus (SYBR Green) kit (Tiangen Biotech, Beijing, China) on the CFX96TM Real-Time system (Bio-Rad Laboratories, Hercules, CA, USA), to validate the changes and trends observed in the microarray analysis. The comparative Ct (2 −ΔΔCt ) method was used to calculate relative fold differences in mRNA expression between HBE p53-/-and HBE p53-wt cells [32,33]. mRNA expression levels were compared using the two-tailed Student's t-test.…”

RNA Profiling Reveals a Common Mechanism of Histone Gene Downregulation and Complementary Effects for Radioprotectants in Response to Ionizing Radiation

“… 26 , 27 Several lncRNAs play key roles in p53-dependent DDR and immune regulation. 28 - 30 Besides other lncRNAs reportedly regulate apoptosis and the cell cycle after DNA damage induction, DNA repair pathways, and DDR protein modification. 31 Despite significant progress in understanding the roles of lncRNAs in the last few years, their specific functions and regulation networks are unclear.…”