Important Pathway Genes Research Articles

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

BackgroundMastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry. Multi-omics approaches enable the comprehensive investigation of the complex interactions between multiple layers of information to provide a more holistic view of disease pathogenesis. Therefore, this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data (mRNA and lncRNA), small RNA sequencing data (miRNA) and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes.ResultsFunctional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis, provided further insights into subclinical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis. The abundant genomic and epigenomic signatures with significant alterations related to subclinical mastitis were observed, including 30,846, 2552, 1276 and 57 differential methylation haplotype blocks (dMHBs), differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs), respectively. Next, 5 factors presenting the principal variation of differential multi-omics signatures were identified. The important roles of Factor 1 (DEG, DEM and DEL) and Factor 2 (dMHB and DEM), in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed. Each of the omics within Factors 1 and 2 explained about 20% of the source of variation in subclinical mastitis. Also, networks of important functional gene sets with the involvement of multi-omics signatures were demonstrated, which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastitis. Furthermore, multi-omics integration enabled the association of the epigenomic regulatory factors (dMHBs, DELs and DEMs) of altered genes in important pathways, such as ‘Staphylococcus aureus infection pathway’ and ‘natural killer cell mediated cytotoxicity pathway’, etc., which provides further insights into mastitis regulatory mechanisms. Moreover, few multi-omics signatures (14 dMHBs, 25 DEGs, 18 DELs and 5 DEMs) were identified as candidate discriminant signatures with capacity of distinguishing subclinical mastitis cows from healthy cows.ConclusionThe integration of genomic and epigenomic data by multi-omics approaches in this study provided a better understanding of the molecular mechanisms underlying subclinical mastitis and identified multi-omics candidate discriminant signatures for subclinical mastitis, which may ultimately lead to the development of more effective mastitis control and management strategies.

LncRNA MIR144HG-derived miR-144 suppresses antibacterial signaling and facilitates bacteria escape in fish

Growing number studies show that lncRNA is an important regulatory factor and plays an irreplaceable role in innate immunity. However, most studies on lncRNA have focused on mammals and it is unknown in lower vertebrates. In this study, we identify a new lncRNA, named MIR144HG, which can have a negative role in antibacterial immunity of Miichthys miiuy caused by Vibrio anguillarum and V. harveyi. MyD88, TAK1 and p65 are very important pathway genes in antibacterial innate immune responses, whether in mammals or lower vertebrates. Here, we found that miR-144–3p could target MyD88, TAK1 and p65, inhibit host antibacterial response and promote bacterial escape. Further studies found that miR-144–3p can be derived by MIR144HG, and finally enhance the inhibitory effect of miR-144–3p on host antibacterial immunity. Moreover, V. anguillarum and V. harveyi are the two most susceptible Gram-negative pathogens in aquaculture, and the economic losses caused by these two bacteria are immeasurable every year. Our results not only elucidate the mechanism of the lncRNA-miRNA-mRNA axis in antibacterial immune responses, but also provide new insights for understanding the impact of lncRNA on host immunity and bacteria escape.

Bioinformatics analysis of the expression and role of microRNA-221-3p in head and neck squamous cell carcinoma

BackgroundHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, associated with a high rate of morbidity and mortality. However, the target genes of miR-221-3p and the underlying mechanism involved in HNSCC are still not clear. Therefore, in the current study, we studied the role of miR-221-3p in the HNSCC.MethodsTissues collected from 48 control and 21 HNSCC patients were processed to check the differential expression of miR-221-3p by RT-qPCR. Overexpression of microRNA-221-3p (miR-221-3p) is significantly correlated to the onset and progression of HNSCC. We also conducted the meta-analysis of the cancer literature from the cancer genome atlas (TCGA) and the Gene Expression Omnibus (GEO) database to estimate the expression of miR-221-3p in HNSCC. The miR-221-3p target genes in the HNSCC were predicted with the miRWalk and TCGA databases, and functionally annotated via the Gene Ontology. Finally, Spearman’s analysis was used to determine the role of the related target genes in important pathways involved in the development of HNSCC.ResultsWe observed a significantly higher expression of miR-221-3p in HNSCC compared to the normal with a summary receiver operating characteristic (sROC) of 0.86(95% Cl: 0.83,0.89). The KEGG and GO comprehensive analysis predicted that miR-221-3p might be involved in the development of HNSCC through the following metabolic pathways, viz. Drug metabolism - cytochrome P450 UGT1A7 and MAOB may be important genes for the role of miR-221-3p.ConclusionBased on bioinformatics analysis, our results indicate that miR-221-3p may be used as a non-invasive and hypersensitive biomarker in the diagnosis. Thus, it can be concluded that miR-221-3p may be an extremely important gene locus involved in the process of the deterioration and eventual tumorigenesis of HNSCC. Hopefully, additional work will validate its usefulness as a target for future clinical research.

Comparative analysis of drought-responsive transcriptomes of sugarcane genotypes with differential tolerance to drought.

Water stress causes considerable yield losses in sugarcane. To investigate differentially expressed genes under water stress, two sugarcane genotypes were subjected to three water-deficit levels (mild, moderate, and severe) and subsequent recovery and leaf transcriptome was generated using Illumina NextSeq sequencing. Among the differentially expressed genes, the tolerant genotype Co 06022 generated 2970 unigenes (p ≤ 0.05, functionally known, non-redundant DEGs) at 2-day stress, and there was a progressive decrease in the expressed genes as the stress period increased with 2109 unigenes at 6-day stress and 2307 unigenes at 10-day stress. There was considerable reduction at recovery with 1334 unigenes expressed at 10days after recovery. However, in the susceptible genotype Co 8021, the number of unigenes expressed at 2 days was lower (2025) than the tolerant genotype and a further reduction was seen at 6-day stress (1552). During recovery, more differentially expressed genes were observed in the susceptible cultivar indicating that the cultivar has to activate more functions/processes to recover from the damage caused by stress. Comparison of DEGs between all stages of stress and recovery in both genotypes revealed that, the commonly up- and down-regulated genes across different stages were approximately double in the tolerant genotype. The most enriched gene ontology classes were heme binding, peroxidase activity and metal ion binding in the biological process and response to oxidative stress, hydrogen peroxide catabolic process and response to stress in the molecular function category. The cellular component was enriched with DEGs involved in extracellular region followed by integral component of membrane. The KEGG pathway analysis revealed important metabolic activities and functionally important genes involved in mitigating water-deficit stress in both the varieties. In addition, several unannotated genes in important pathways were detected and together may provide novel insights into water-deficit tolerance mechanisms in sugarcane. The reliability of the observed expression patterns was confirmed by qRT-PCR. The results of this study will help to identify useful genes for improving drought tolerance in sugarcane.

Comparative transcriptome analysis indicates that a core transcriptional network mediates isonuclear alloplasmic male sterility in wheat (Triticum aestivum L.)

BackgroundCytoplasmic male sterility (CMS) plays a crucial role in the utilization of heterosis and various types of CMS often have different abortion mechanisms. Therefore, it is important to understand the molecular mechanisms related to anther abortion in wheat, which remain unclear at present.ResultsIn this study, five isonuclear alloplasmic male sterile lines (IAMSLs) and their maintainer were investigated. Cytological analysis indicated that the abortion type was identical in IAMSLs, typical and stainable abortion, and the key abortive period was in the binucleate stage. Most of the 1,281 core shared differentially expressed genes identified by transcriptome sequencing compared with the maintainer in the vital abortive stage were involved in the metabolism of sugars, oxidative phosphorylation, phenylpropane biosynthesis, and phosphatidylinositol signaling, and they were downregulated in the IAMSLs. Key candidate genes encoding chalcone--flavonone isomerase, pectinesterase, and UDP-glucose pyrophosphorylase were screened and identified. Moreover, further verification elucidated that due to the impact of downregulated genes in these pathways, the male sterile anthers were deficient in sugar and energy, with excessive accumulations of ROS, blocked sporopollenin synthesis, and abnormal tapetum degradation.ConclusionsThrough comparative transcriptome analysis, an intriguing core transcriptome-mediated male-sterility network was proposed and constructed for wheat and inferred that the downregulation of genes in important pathways may ultimately stunt the formation of the pollen outer wall in IAMSLs. These findings provide insights for predicting the functions of the candidate genes, and the comprehensive analysis of our results was helpful for studying the abortive interaction mechanism in CMS wheat.