Dataset Information

Identification of circRNA-Associated-ceRNA Networks Involved in Milk Fat Metabolism under Heat Stress.

ABSTRACT: Summer temperatures are generally high in Southern China, and cows are likely to suffer a heat stress reaction. Heat stress will have a negative impact on the performance of dairy cows; however, the mechanism by which high temperature affects lactation is not clear. CircRNA is a type of non-coding RNA discovered in recent years, which performs a crucial function in many biological activities. However, the effects of circRNA on lactation function of dairy cows under heat stress is unknown. The present study aimed to explore the expression levels of circRNA in the mammary gland tissue of cows under heat stress. Firstly, we collected blood and milk samples of summer and winter cows and evaluated lactation performance using serum indicators, milk production, and milk composition. Incorporating the calculation of the temperature and humidity index, we conformed the heat stress status of cows in summer. Heat stress increased the concentration of HSP70 and decreased the concentration of SOD and PRL. Heat stress not only reduced milk yield but also affected milk quality, with milk lactose and milk protein decreasing with increased temperature. The analysis of the fatty acid composition in summer milk found significantly reduced concentrations of unsaturated fatty acids, especially long-chain unsaturated fatty acids. Sequencing of the cow's mammary gland transcriptome revealed that compared to the appropriate temperature (ST) group, the heat stress (HS) group had a total of 2204 upregulated and 3501 downregulated transcripts. GO enrichment and KEGG pathway analysis showed that these genes were mainly related to milk fat metabolism. In addition, 19 upregulated and 19 downregulated circRNA candidates were found in response to heat stress. We used Pearson's test to establish the correlation of circRNA-mRNA and identified four pairs of circRNA-miRNA networks between four circRNAs, six miRNAs, and the CD36 gene. In this study, we revealed the possible role of circRNAs in lactation of dairy cows and identified that circRNA-miRNA-mRNA networks might exist in the cow's mammary glands, providing valuable experience for dairy lactation and milk quality.

SUBMITTER: Wang D

PROVIDER: S-EPMC7312917 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Identification of circRNA-Associated-ceRNA Networks Involved in Milk Fat Metabolism under Heat Stress.

Wang Dongyang D Chen Zujing Z Zhuang Xiaona X Luo Junyi J Chen Ting T Xi Qianyun Q Zhang Yongliang Y Sun Jiajie J

International journal of molecular sciences 20200611 11

Summer temperatures are generally high in Southern China, and cows are likely to suffer a heat stress reaction. Heat stress will have a negative impact on the performance of dairy cows; however, the mechanism by which high temperature affects lactation is not clear. CircRNA is a type of non-coding RNA discovered in recent years, which performs a crucial function in many biological activities. However, the effects of circRNA on lactation function of dairy cows under heat stress is unknown. The pr ...[more]

PMID: 32545169

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Project description:Heat stress represents a major environmental factor that negatively affects the health and performance of dairy cows, causing huge economic losses to the dairy industry. Identifying and selecting animals that are thermotolerant is an attractive alternative for reducing the negative effects of heat stress on dairy cattle performance. As such, the objectives of the present study were to estimate genetic components of milk yield, fat yield, and protein yield considering heat stress and to perform whole-genome scans and a subsequent gene-set analysis for identifying candidate genes and functional gene-sets implicated in milk production under heat stress conditions. Data consisted of about 254k test-day records from 17,522 Holstein cows. Multi-trait repeatability test day models with random regressions on a function of temperature-humidity index (THI) values were used for genetic analyses. The models included herd-test-day and DIM classes as fixed effects, and general and thermotolerance additive genetic and permanent environmental as random effects. Notably, thermotolerance additive genetic variances for all milk traits increased across parities suggesting that cows become more sensitive to heat stress as they age. In addition, our study revealed negative genetic correlations between general and thermotolerance additive effects, ranging between -0.18 to -0.68 indicating that high producing cows are more susceptible to heat stress. The association analysis identified at least three different genomic regions on BTA5, BTA14, and BTA15 strongly associated with milk production under heat stress conditions. These regions harbor candidate genes, such as HSF1, MAPK8IP1, and CDKN1B that are directly involved in the cellular response to heat stress. Moreover, the gene-set analysis revealed several functional terms related to heat shock proteins, apoptosis, immune response, and oxidative stress, among others. Overall, the genes and pathways identified in this study provide a better understanding of the genetic architecture underlying dairy cow performance under heat stress conditions. Our findings point out novel opportunities for improving thermotolerance in dairy cattle through marker-assisted breeding.

Project description:BACKGROUND:The traditional Chinese medicine prescription, Qianggan formula have been confirmed to be effective on non-alcoholic steatohepatitis (NASH), however, the underlying molecular mechanisms remain obscure. METHODS:Thirty-six male C57BL/6 mice were randomly divided into three groups: normal chow diet group; methionine-and-choline-deficient diet (MCD) group, and Qianggan extract (QG) intervention group (0.4?g/kg daily) that fed with MCD. The efficacy of QG was biochemically and histologically evaluated. The expression profiles of messenger ribonucleic acids (mRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) were examined using microarray and verified by RT-qPCR. RESULTS:QG significantly improved the phenotypic characteristics of NASH, as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) levels and liver inflammatory cytokines were significantly decreased. By the cutoff of a 1.5-fold change and P?<?0.05, 6193 mRNAs, 5692 lncRNAs and 4843 circRNAs were identified as differentially expressed between the MCD and normal groups, and 514 mRNAs, 1182 lncRNAs and 443 circRNAs were identified as differentially expressed between the QG and MCD groups. The intersections (244 mRNAs, 259 lncRNAs and 98 circRNAs) among the three groups were chosen for analysis. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that most overlapping mRNAs were related to immune functions such as natural-killer-cell-mediated cytotoxicity, intestinal immune network for IgA production, and T cell receptor signaling pathway. Pathway interactions, protein-protein interactions and molecular complex detection (MCODE) analysis identified numerous immune-related hub genes e.g. natural cytotoxicity triggering receptor 1(Ncr1), C-X-C motif chemokine ligand 9 (Cxcl9), Klra1, and Cd28. Finally, two lncRNAs (Sngh1 and Slc36a3os) and four circRNAs (circ_0009029, circ_0004572, circ_0009212 and circ_0009453) in competing endogenous RNA (ceRNA) networks were constructed by Cytoscape, and immune-related mRNAs (e.g., Cd28, Cd8a, Il15, and Klrk1) were involved in the ceRNA networks. CONCLUSIONS:LncRNA and circRNA-associated immune ceRNA networks might be the targets of QG in alleviating NASH, and our work may provide valuable clues for exploring the mechanisms underlying the effect of QG.

Project description:Background: Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease. The characteristic pathologies include extracellular senile plaques formed by β-amyloid protein deposition, neurofibrillary tangles formed by hyperphosphorylation of tau protein, and neuronal loss with glial cell hyperplasia. Circular RNAs (circRNAs) are rich in miRNA-binding sites (miRNA response elements, MREs), which serve as miRNA sponges or competitive endogenous RNAs (ceRNAs). Although several research groups have identified dysregulated circRNAs in the cerebral cortex of SAMP8 mice or APP/PS1 mice using deep RNA-seq analysis, we need to further explore circRNA expression patterns, targets, functions and the signaling pathways involved in the pathogenesis of AD and in particular the hippocampal circRNA expression profiles in AD. Methods: We used deep RNA sequencing to investigate circRNA-ceRNA network patterns in the hippocampus of APP/PS1 mice. Results: In our study, 70 dysregulated circRNAs, 39 dysregulated miRNAs and 121 dysregulated mRNAs were identified between the APP/PS1 group and the wild-type group at 8 months in the hippocampus of the mice. Through correlation analysis, we identified 11 dysregulated circRNAs, 7 dysregulated miRNAs and 8 dysregulated mRNAs forming 16 relationships in the circRNA-miRNA-mRNA regulatory network. Gene ontology (GO) analysis indicated that the dysregulated circRNAs were most enriched in biological metabolic processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the dysregulation of circRNAs was enriched in the cGMP-PKG signaling pathway, cAMP signaling pathway, Hippo signaling pathway, platelet activation, long-term potentiation and axon guidance. In addition, our findings preliminarily verified that the novel_circ_0003012/mmu-miR-298-3p/Smoc2 signaling axis may regulate the pathophysiology of AD by affecting the cGMP-PKG signaling pathway. Conclusions: These newly identified circRNAs in networks and signaling pathways reveal potential diagnostic or therapeutic targets for AD.

Dataset Information

Identification of circRNA-Associated-ceRNA Networks Involved in Milk Fat Metabolism under Heat Stress.

Publications

Identification of circRNA-Associated-ceRNA Networks Involved in Milk Fat Metabolism under Heat Stress.

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