scholarly journals Deep Sequencing of Guinea Pig (Cavia Porcellus) Lung Small RNAs Reveals Differential Expression of microRNAs between Non-infected and BCG-Infected Lungs

Author(s):  
Xiaoqi jing ◽  
Biqiong Jiang ◽  
Long Cheng ◽  
Yong Li

Abstract Background: Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection remains a major public health burden worldwide. It has been well documented that a group of small noncoding RNAs, microRNAs (miRNAs) are involved in the development and pathogenesis many diseases, including the TB. Guinea pigs are considered as one of the best animal models for biomedical research in TB, the potential roles of miRNAs in the innate immune regulation of guinea pig lung against Mtb infection are not well understood. Methods: In this study, we investigated the differential expression of miRNA profiles between the un-infected lungs and Mycobacterium bovis bacillus Calmette-Guérin (BCG)-infected lungs of guinea pigs via deep sequencing and bioinformatics analysis. Results: A total of 2508 miRNAs were identified, among them 1187 were conserved miRNAs and 56 were novel miRNAs in the uninfected lungs, and 1202 were identified as conserved miRNAs and 63 were novel miRNAs in the BCG-infected lungs. Interestingly, comparison analysis further identified 902 co-expressed miRNAs and 585 distinct miRNAs between these two groups. Of the 15 most abundantly conserved miRNAs in guinea pig lungs, which belong to 7 miRNA families, including miR23, miR29, miR145, miR320, miR378, miR451, and miR423. 13 of these 15 most abundant miRNAs were significantly downregulated and 2 of them were significantly upregulated in the BCG-infected lungs. Individually, miRNA Let-7f-5p, let-7f, let-7-5p and let-7b-5p were the most abundant in both profiles of the non-infected and BCG-infected guinea pig lungs. The predicted target genes of specific miRNAs found in guinea pig lungs were involved in regulation signaling pathways related to immune responses, including Toll-like receptors (TLRs), nuclear factor (NF)-kappa B, Wnt, mitogen-activated protein kinase (MAPK), and transforming growth factor (TGF)-beta signaling, as well as related to autophagy signaling mTOR and apoptotic molecule p53. Conclusions: These data of comprehensive analysis of miRNA transcriptome demonstrated the differential expression profiles of miRNAs during M. tuberculosis infection of guinea pig lungs. These results could facilitate the future exploitation of the roles of miRNAs in regulation of immune responses to M. tuberculosis infection using the guinea pig model.

2021 ◽  
Vol 12 ◽  
Author(s):  
Simone Howard ◽  
Shakyra Richardson ◽  
Ifeyinwa Benyeogor ◽  
Yusuf Omosun ◽  
Kamran Dye ◽  
...  

Vaccine-induced immune responses following immunization with promising Chlamydia vaccines protected experimental animals from Chlamydia-induced upper genital tract pathologies and infertility. In contrast, primary genital infection with live Chlamydia does not protect against these pathologies. We hypothesized that differential miRNA profiles induced in the upper genital tracts (UGT) of mice correlate with the disparate immunity vs. pathologic outcomes associated with vaccine immunization and chlamydial infection. Thus, miRNA expression profiles in the UGT of mice after Chlamydia infection (Live EB) and immunization with dendritic cell (DC)-based vaccine (DC vaccine) or VCG-based vaccine (VCG vaccine) were compared using the NanoString nCounter Mouse miRNA assay. Of the 602 miRNAs differentially expressed (DE) in the UGT of immunized and infected mice, we selected 58 with counts >100 and p-values < 0.05 for further analysis. Interestingly, vaccine immunization and Chlamydia infection induced the expression of distinct miRNA profiles with a higher proportion in vaccine-immunized compared to Chlamydia infected mice; DC vaccine (41), VCG vaccine (23), and Live EB (15). Hierarchical clustering analysis showed notable differences in the uniquely DE miRNAs for each experimental group, with DC vaccine showing the highest number (21 up-regulated, five down-regulated), VCG vaccine (two up-regulated, five down-regulated), and live EB (two up-regulated, four down-regulated). The DC vaccine-immunized group showed the highest number (21 up-regulated and five down-regulated compared to two up-regulated and four down-regulated in the live Chlamydia infected group). Pathway analysis showed that the DE miRNAs target genes that regulate several biological processes and functions associated with immune response and inflammation. These results suggest that the induction of differential miRNA expression plays a significant role in the disparate immunity outcomes associated with Chlamydia infection and vaccination.


2020 ◽  
Author(s):  
Qing Xia ◽  
Qiuling Li ◽  
Shangquan Gan ◽  
Xiaofei Guo ◽  
Xiaosheng Zhang ◽  
...  

Abstract Background Long non-coding RNAs (lncRNAs) can play important roles in uterine and ovarian functions. However, little researches have been done on the role of lncRNAs in the adrenal gland of sheep. Herein, RNA sequencing was used to compare and analyze gene expressions in adrenal tissues between FecB ++ (WW) and FecB BB (MM) sheep in the follicular and luteal phases and key lncRNAs and genes associated with reproduction were identified. Results In MM sheep, 38 lncRNAs and 545 mRNAs were differentially expressed in the adrenal gland between the luteal and follicular phases; In WW sheep, 30 differentially expressed lncRNAs and 210 mRNAs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that differentially expressed lncRNAs and their target genes are mainly involved in the circadian rhythm, the mitogen activated protein kinase, thyroid, ovarian steroidogenesis and transforming growth factor beta signaling pathways. Key lncRNAs can regulate reproduction by modulating genes involved in these signaling pathways and biological processes. Specifically, XLOC_254761 , XLOC_357966 , 105614839 and XLOC_212877 targeting CREB1 , PER3 , SMAD1 and TGFBR2 , respectively, appear to play key regulatory roles. Conclusion These results broaden our understanding of lncRNAs in adrenal gland of sheep and provide new insights into the molecular mechanisms underlying sheep reproduction.


2021 ◽  
Author(s):  
Yingying Zhou ◽  
Yuqing Huang ◽  
Tielong Chen ◽  
Wenjia Hu ◽  
Xiaoping Chen ◽  
...  

Abstract Background: Many studies have shown that long noncoding RNAs (lncRNAs) derived from the host and human immunodeficiency virus (HIV) itself play important roles in virus-host interactions and viral pathogenesis. To identify potential key lncRNAs in the regulation of HIV pathogenesis, transcriptome analysis of peripheral blood mononuclear cells (PBMCs), which were derived from 6 HIV/acquired immunodeficiency syndrome (AIDS) subjects pre-HAART and post-HAART with effective control of plasma viremia (<20 HIV RNA copies/ml) and 6 healthy subjects, was performed by RNA sequencing (RNA-seq).Results: We identified a total of 974 lncRNAs whose expression levels were restored to normal after ART therapy. The results of the cis-acting analysis showed that only six lncRNAs have cis-regulated target genes, among which the target gene RP11-290F5.1, interferon regulatory factors 2 (IRF2), could promote HIV replication. We also identified lncRNA CTB-119C2.1, which regulates most mRNAs with differential expression between pre- and post-HAART, and the differences were significant. We selected lncRNA CTB-119C2.1 for qRT–PCR verification, and the results were consistent with those of RNA-seq. RAB3A and GADD45A, two of the lncRNA CTB-119C2.1-associated genes, have been shown to be associated with HIV infection. KEGG analysis of lncRNA CTB-119C2.1-associated genes revealed that most of the genes are involved in the p53 signaling pathway or pathways related to cell circulation and DNA replicationConclusion: In this study, we used RNA-seq to systematically compare the expression profiles of lncRNAs in HIV subjects between untreated and treated time points. We successfully identified some lncRNAs with differential expression during certain periods (no HIV infection, HIV infection before treatment, and after treatment). Their expression is associated with viral loads, and some of their regulating genes were found to be involved in HIV pathogenesis through bioinformatic analysis. These findings could help to reveal the underlying molecular mechanism of the progression of AIDS.


2022 ◽  
Vol 12 ◽  
Author(s):  
Xiaodong Zhao ◽  
Zhibin Ji ◽  
Rong Xuan ◽  
Aili Wang ◽  
Qing Li ◽  
...  

The liver is the largest digestive gland in goats with an important role in early metabolic function development. MicroRNAs (miRNA) are crucial for regulating the development and metabolism in the goat liver. In the study, we sequenced the miRNAs in the liver tissues of the goat kid to further research their regulation roles in early liver development. The liver tissues were procured at 5-time points from the Laiwu black goats of 1 day (D1), 2 weeks (W2), 4 weeks (W4), 8 weeks (W8), and 12 weeks (W12) after birth, respectively with five goats per time point, for a total of 25 goats. Our study identified 214 differential expression miRNAs, and the expression patterns of 15 randomly selected miRNAs were examined among all five age groups. The Gene ontology annotation results showed that differential expression miRNA (DE miRNA) target genes were significantly enriched in the fatty acid synthase activity, toxin metabolic process, cell surface, and antibiotic metabolic process. The KEGG analysis result was significantly enriched in steroid hormone synthesis and retinol metabolism pathways. Further miRNA-mRNA regulation network analysis reveals 9 differently expressed miRNA with important regulation roles. Overall, the DE miRNAs were mainly involved in liver development, lipid metabolism, toxin related metabolism-related biological process, and pathways. Our results provide new information about the molecular mechanisms and pathways in the goat kid liver development.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jufeng Zhang ◽  
Xia Luo ◽  
Huiming Li ◽  
Ling Deng ◽  
Ying Wang

Colorectal cancer (CRC) is one of the most common malignancies resulting in high mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor which is frequently activated and aberrantly expressed in CRC. MicroRNAs (miRNAs) are a class of small noncoding RNAs which play important roles in many cancers. However, little is known about the global miRNA profiles mediated by STAT3 in CRC cells. In the present study, we applied RNA interference to inhibit STAT3 expression and profiled the miRNA expression levels regulated by STAT3 in CRC cell lines with deep sequencing. We found that 26 and 21 known miRNAs were significantly overexpressed and downexpressed, respectively, in the STAT3-knockdown CRC cell line SW480 (SW480/STAT3-siRNA) compared to SW480 transfected with scrambled siRNAs (SW480/siRNA-control). The miRNA expression profiling was then validated by quantitative real-time PCR for selected known miRNAs. We further predicted the putative target genes for the dysregulated miRNAs and carried out functional annotation including GO enrichment and KEGG pathway analysis for selected miRNA targets. This study directly depicts STAT3-mediated miRNA profiles in CRC cells, which provides a possible way to discover biomarkers for CRC therapy.


2008 ◽  
Vol 19 (4) ◽  
pp. 1519-1528 ◽  
Author(s):  
Haixia Wang ◽  
Qing Xu ◽  
Fang Xiao ◽  
Yong Jiang ◽  
Zhenguo Wu

We and others previously showed that p38 mitogen-activated protein kinase is indispensable for myogenic differentiation. However, it is less clear which of the four p38 isoforms in the mouse genome participates in this process. Using C2C12 myogenic cells as a model, we showed here that p38α, β, and γ are expressed with distinct expression patterns during differentiation. Knockdown of any of them by small interfering RNA inhibits myogenic differentiation, which suggests that the functions of the three p38 isoforms are not completely redundant. To further elucidate the unique role of each p38 isoform in myogenic differentiation, we individually knocked down one p38 isoform at a time in C2C12 cells, and we compared the whole-genome gene expression profiles by microarrays. We found that some genes are coregulated by all three p38 isoforms, whereas others are uniquely regulated by one particular p38 isoform. Furthermore, several novel p38 target genes (i.e., E2F2, cyclin D3, and WISP1) are found to be required for myogenin expression, which provides a molecular basis to explain why different p38 isoforms are required for myogenic differentiation.


2014 ◽  
Author(s):  
Chunyu Bai ◽  
Xiangchen Li ◽  
Yuhua Gao ◽  
Taofeng Lu ◽  
Kunfu Wang ◽  
...  

MicroRNAs (miRNAs) are small noncoding RNAs that bind to the 3?-UTR of mRNAs and function mainly in post-transcriptional regulation. MiRNAs have been implicated to play roles in organ development, including that of the pancreas. Many miRNAs, such as miR-375, miR-124, miR-7, miR-21 and miR-221, have been shown to regulate insulin production as well as insulin secretion. However, it is not known whether miRNAs can regulate insulin secretion via the control of intracellular Ca2+ in pancreatic beta cells. In this research, expression profiles of miRNAs and mRNAs were investigated using RNA-sequencing and microarray analysis in chicken pancreatic nestin-positive progenitor cells and differentiated pancreatic beta cells. A number of miRNAs were up-regulated after differentiation of progenitors into beta cells, which regulate cell signaling pathways to control cell function. miR-223 and miR146a were shown to promote insulin secretion from pancreatic beta cells by regulating the concentration of intracellular Ca2+ via the down-regulation of their target genes.


2020 ◽  
Author(s):  
Qing Xia ◽  
Qiuling Li ◽  
Shangquan Gan ◽  
Xiaofei Guo ◽  
Xiaosheng Zhang ◽  
...  

Abstract Background: Long non-coding RNAs (lncRNAs) can play important roles in uterine and ovarian functions. However, little researches have been done on the role of lncRNAs in the adrenal gland of sheep. Herein, RNA sequencing was used to compare and analyze gene expressions in adrenal tissues between follicular phases and luteal phases in FecBBB (MM) and FecB++ (WW) sheep, respectively, and differentially expressed lncRNAs and genes associated with reproduction were identified.Results: In MM sheep, 38 lncRNAs and 545 mRNAs were differentially expressed in the adrenal gland between the luteal and follicular phases; In WW sheep, 513 differentially expressed lncRNAs and 2481 mRNAs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that differentially expressed lncRNAs and their target genes are mainly involved in the circadian rhythm, the mitogen activated protein kinase, thyroid, ovarian steroidogenesis and transforming growth factor beta signaling pathways. Differentially expressed lncRNAs can regulate reproduction by modulating genes involved in these signaling pathways and biological processes. Specifically, XLOC_254761, XLOC_357966, 105614839 and XLOC_212877 targeting CREB1, PER3, SMAD1 and TGFBR2, respectively, appear to play key regulatory roles. Conclusion: These results broaden our understanding of lncRNAs in adrenal gland of sheep and provide new insights into the molecular mechanisms underlying sheep reproduction.


Epigenomics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 825-842 ◽  
Author(s):  
Sirui Huang ◽  
Zhenlin Tang ◽  
Yuheng Wang ◽  
Danliang Chen ◽  
Jinhua Li ◽  
...  

Aim: To assess differential expression profiles of miRNAs in exosomes derived from human peripheral blood (PB) and umbilical cord blood (UCB). Materials & methods: Small RNA sequencing was performed to characterize the miRNA expression in plasma exosomes processed from UCB of five healthy newborns and PB of five normal adult volunteers, and differentially expressed miRNAs were further analyzed. Results: A total of 65 exosomal miRNAs, including 46 upregulated and 19 downregulated, showed differential expression between UCB and PB. Target genes of these miRNAs were mainly enriched in signaling pathways associated with pregnancy, cancers, cell mobility and nervous system. Conclusion: Exosomal miRNAs may have essential roles in the biological functions of UCB, suggesting the therapeutic and biomarker potentials of exosomes in UCB.


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