Long Noncoding RNA Profiles Research Articles

Expression Profiles of Long Noncoding RNAs and Messenger RNAs in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious disorder of the central nervous system with a high disability rate. Long noncoding RNAs (lncRNAs) are reported to mediate many biological processes. The aim of this study was to explore lncRNA and mRNA expression profiles and functional networks after SCI. Differentially expressed genes between SCI model rats and sham controls were identified by microarray assays and analyzed by functional enrichment. Key lncRNAs were identified using a support vector machine- (SVM-) recursive feature elimination (RFE) algorithm. A trans and cis regulation model was used to analyze the regulatory relationships between lncRNAs and their targets. An lncRNA-related ceRNA network was established. We identified 5465 differentially expressed lncRNAs (DE lncRNAs) and 8366 differentially expressed mRNAs (DE mRNAs) in the SCI group compared with the sham group (fold change > 2.0, p < 0.05). Four genes were confirmed by qRT-PCR which were consistent with the microarray data. GSEA analysis showed that most marked changes occurred in pathways related to immune inflammation and nerve cell function, including cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and GABAergic synapse. Enrichment analysis identified 30 signaling pathways, including those associated with immune inflammation response. A total of 40 key lncRNAs were identified using the SVM-RFE algorithm. A key lncRNA-mRNAs coexpression network was generated for 230 951 lncRNA-mRNA pairs with half showing positive correlations. Several key DE lncRNAs were predicted to have "cis"- or "trans"-regulated target genes. The transcription factors, Sp1, JUN, and SOX10, may regulate the interaction between XR_001837123.1 and ETS 1. In addition, five pairs of ceRNA regulatory sequences were constructed. Many mRNAs and lncRNAs were found to be dysregulated after SCI. Bioinformatic analysis showed that DE lncRNAs may play crucial roles in SCI. It is anticipated that these findings will provide new insights into the underlying mechanisms and potential therapeutic targets for SCI.

Construction of a potentially functional lncRNA-miRNA-mRNA network in sepsis by bioinformatics analysis.

Objective: Sepsis is a common disease in internal medicine, with a high incidence and dangerous condition. Due to the limited understanding of its pathogenesis, the prognosis is poor. The goal of this project is to screen potential biomarkers for the diagnosis of sepsis and to identify competitive endogenous RNA (ceRNA) networks associated with sepsis. Methods: The expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) were derived from the Gene Expression Omnibus (GEO) dataset. The differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) were screened by bioinformatics analysis. DEmRNAs were analyzed by protein-protein interaction (PPI) network analysis, transcription factor enrichment analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Set Enrichment Analysis (GSEA). After the prediction of the relevant database, the competitive ceRNA network is built in Cytoscape. The gene-drug interaction was predicted by DGIgb. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm five lncRNAs from the ceRNA network. Results: Through Venn diagram analysis, we found that 57 DElncRNAs, 6 DEmiRNAs and 317 DEmRNAs expressed abnormally in patients with sepsis. GO analysis and KEGG pathway analysis showed that 789 GO terms and 36 KEGG pathways were enriched. Through intersection analysis and data mining, 5 key KEGG pathways and related core genes were revealed by GSEA. The PPI network consists of 247 nodes and 1,163 edges, and 50 hub genes are screened by the MCODE plug-in. In addition, there are 5 DElncRNAs, 6 DEmiRNAs and 28 DEmRNAs in the ceRNA network. Drug action analysis showed that 7 genes were predicted to be molecular targets of drugs. Five lncRNAs in ceRNA network are verified by qRT-PCR, and the results showed that the relative expression of five lncRNAs was significantly different between sepsis patients and healthy control subjects. Conclusion: A sepsis-specific ceRNA network has been effectively created, which is helpful to understand the interaction between lncRNAs, miRNAs and mRNAs. We discovered prospective sepsis peripheral blood indicators and proposed potential treatment medicines, providing new insights into the progression and development of sepsis.

Expression profile of long non-coding RNAs in the intestine of black rockfish Sebastes schlegelii in response to Edwardsiella tarda infection

Expression profile of long non-coding RNAs in the intestine of black rockfish Sebastes schlegelii in response to Edwardsiella tarda infection

Transcriptional profiling of long non-coding RNAs regulating fruit cracking in Punica granatum L. under bagging.

Fruit cracking tremendously damages the appearance of fruit, easily leads to pathogen invasion, greatly reduces the marketability and causes immense economic losses. The pivotal role of long non-coding RNAs (lncRNAs) in diverse biological processes has been confirmed, while the roles of lncRNAs underlying fruit cracking remain poorly understood. In this study, the incidence of fruit cracking was 7.26% under the bagging treatment, the control group was 38.11%, indicating that bagging considerably diminished the fruit cracking rate. LncRNA libraries for fruit cracking (FC), fruit non-cracking (FNC) and fruit non-cracking under bagging (FB) in pomegranate (Punica granatum L.) were performed and analysed via high-throughput transcriptome sequencing. A total of 3194 lncRNAs were obtained with a total length of 4898846 nt and an average length of 1533.77 nt in pomegranate. We identified 42 differentially expressed lncRNAs (DELs) and 137 differentially expressed mRNAs (DEGs) in FC vs FNC and 35 DELs and 160 DEGs in FB vs FC that formed co-expression networks respectively, suggesting that there are involved in phytohormone signaling pathway, lignin catabolic process, lipid transport/binding, cutin biosynthetic process and cell wall organization. We also found that 18 cis-acting DELs regulated 18 target genes, and 10 trans-acting DELs regulated 24 target genes in FC vs FNC, 23 DELs regulate 23 target genes for the cis-acting lncRNAs and 12 DELs regulated 36 target genes in FB vs FC, which provides an understanding for the regulation of the fruit cracking. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results demonstrated that DELs participated in calcium ion binding, glycerophospholipid metabolism, flavonoid biosynthetic process, cell wall biogenesis, xyloglucan metabolic process, hormone signal transduction and starch and sucrose metabolism. Our findings provide new insights into the roles of lncRNAs in regulating the fruit cracking and lay the foundation for further improvement of pomegranate quality.

The stem cell-specific long non-coding RNAs in leukemia.

Leukemia is defined as a heterogeneous group of hematological cancers whose prevalence is on the rise worldwide. Despite the large body of studies, the etiology of leukemia has not been fully elucidated. Leukemia stem cells (LSCs) are a subpopulation of cancer cells that sustain the growth of the leukemic clone and are the main culprit for the maintenance of the neoplasm. In contrast to most leukemia cells, LSCs are resistant to chemo- and radiotherapy. Several recent studies demonstrated the altered expression profile of long non-coding RNAs (lncRNAs) in LSCs and shed light on the role of lncRNAs in the survival, proliferation, and differentiation of LSCs. LncRNAs are transcripts longer than 200 nucleotides that are implicated in several cellular and molecular processes such as gene expression, apoptosis, and carcinogenesis. Likewise, lncRNAs have shown a prognostic marker in leukemia patients and represent novel treatment options. Herein, we review the current knowledge concerning lncRNAs' implication in the pathogenesis of LSCs and discuss their prognostic, diagnostic, and therapeutic potential.

MRNA and lncRNA expression profiles of liver tissues in children with biliary atresia

Progressive liver fibrosis is the most common phenotype in biliary atresia (BA). A number of pathways contribute to the fibrosis process so comprehensive understanding the mechanisms of liver fibrosis in BA will pave the way to improve patient's outcome after operation. In this study, the differentially expressed profiles of mRNAs and long non-coding RNAs from BA and choledochal cyst (CC) liver tissues were investigated and analyzed, which may provide potential clues to clarify hepatofibrosis mechanism in BA. A total of two BA and two CC liver tissue specimens were collected, the expression level of mRNAs and lncRNAs was detected by RNA sequencing. Differentially expressed mRNAs (DEmRNAs) were functionally annotated and protein-protein interaction networks (PPI) was established to predict the biological roles and interactive relationships. Differentially expressed lncRNAs (DElncRNAs) nearby targeted DEmRNA network and DElncRNA-DEmRNA co-expression network were constructed to further explore the roles of DElncRNAs in BA pathogenesis. The expression profiles of significant DEmRNAs were validated in Gene Expression Omnibus database. A total of 2,086 DEmRNAs and 184 DElncRNAs between BA and CC liver tissues were obtained. DEmRNAs were enriched in 521 Gene Ontology terms and 71 Kyoto Encyclopedia of Genes and Genomes terms which were mainly biological processes and metabolic pathways related to immune response and inflammatory response. A total of five hub proteins (TYRO protein tyrosine kinase binding protein, C-X-C motif chemokine ligand 8, pleckstrin, Toll-like receptor 8 and C-C motif chemokine receptor 5) were found in the PPI networks. A total of 31 DElncRNA-nearby-targeted DEmRNA pairs and 2,337 DElncRNA-DEmRNA co-expression pairs were obtained. The expression of DEmRNAs obtained from RNA sequencing were verified in GSE46960 dataset, generally. The present study identified key genes and lncRNAs participated in BA associated liver fibrosis, which may present a new avenue for understanding the patho-mechanism for hepatic fibrosis in BA.

Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma.

Novel biomarkers are highly required for the diagnosis and predicting prognosis of hepatocellular carcinoma (HCC). In this study, we investigated the profiles of long non-coding RNAs (lncRNAs) obtained from the peripheral blood mononuclear cells (PBMCs) of patients with HCC and PBMCs from a co-culture model using transcriptomic analysis. The differentially expressed lncRNAs (DElncRNAs) were then characterized and integrated as cancer-induced lncRNAs. Among them, three up-regulating DElncRNAs including MIR4435-2HG, SNHG9 and lnc-LCP2-1 and one down-regulating, lnc-POLD3-2, were identified. The functional analysis showed that these enriched lncRNAs were mainly associated with carcinogenesis and immune responses. Following further validation in PBMCs samples (100 HBV-related HCC, 100 chronic hepatitis B and 100 healthy controls), MIR4435-2HG, lnc-POLD3-2 and their combination were revealed to be sensitive biomarkers in discriminating HCC from non-HCC (AUROC = 0.78, 0.80, and 0.87, respectively), particularly among individuals with normal serum alpha-fetoprotein levels. Additionally, high circulating SNHG9 expression was shown to be an independent prognostic factor of overall survival in patients with HCC. These results indicate that determining these lncRNAs in PBMCs could serve as novel diagnostic and prognostic biomarkers for HBV-related HCC.

MRNA, lncRNA and Circular RNA Expression Profiles in Granulosa Cells of Infertile Women with Ovarian Endometriosis.

To explore the expression profiles of mRNAs, long-noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and construct the competitive endogenous RNA networks in granulosa cells (GCs) of infertile women with ovarian endometriosis. RNA sequencing was conducted for RNA expression profiling from GCs of five women with ovarian endometriosis and five with tubal factor infertility. The differential expression of mRNAs, lncRNAs and circRNAs was compared. Then, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed. Finally, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to determine the role of the differential expression of mRNA. A total of 12,498 mRNAs, 724 lncRNAs and 2269 circRNAs were identified in ovarian endometriosis and controls. 37 mRNAs, 51 lncRNAs and 101 circRNAs were detected to be differentially expressed in women with ovarian endometriosis. Ten lncRNAs and 22 differentially expressed mRNAs were selected to build the lncRNA-miRNA-mRNA network, while 12 circRNAs and four differentially expressed mRNAs were selected to build the circRNA-miRNA-mRNA network. GO analysis suggested that the differentially expressed mRNAs were mainly involved in regulation of cell differentiation, cell cycle while KEGG pathway analysis showed that pathways involved in the MAPK signaling pathway and FoxO signaling pathway were enriched with differentially upregulated mRNAs. We generated mRNAs, lncRNAs and circRNAs expression profiles and identified differentially expressed RNAs of GCs in infertile women with ovarian endometriosis. These findings provide a basis for further understanding of the underlying etiology of endometriosis-related infertility.

LncRNA-mRNA Expression Profiles of Osteoclast After Conditional Knockout HIF-1α.

Background: Osteoclasts, which are multinucleated cells formed by monocyte fusion, play a key role in bone resorption. Hypoxia-inducible factor (HIF)-1α is vital for the development of osteoclasts in hypoxic environments and during bone resorption. However, additional research is required to further study the HIF-1α-dependent regulation of osteoclast differentiation at the genetic level. Methods: In our study, RNA sequencing (RNA-seq) was used to identify the expression profiles of long noncoding RNAs (lncRNAs) and mRNAs in conditional HIF-1α-knockout osteoclasts. Results: A total of 1,320 mRNAs and 95 lncRNAs were differentially expressed. The expression of lncRNAs MSTRG.7566.12 and MSTRG.31769.2 were strongly negatively correlated with that of Mmp9, Ctsk, etc. Conclusion: Our research provides a basis for further understanding the role of mRNAs and lncRNAs in conditional HIF-1α-knockout osteoclasts, and many of these molecules may be potential targets for treating bone diseases related to HIF-1α.

Expression profiles of long non-coding RNAs in neurogenic bladder of spinal cord injured rats: a transcriptomic analysis.

BackgroundGrowing evidence has indicated that long non-coding RNAs (lncRNAs) are important regulators of pathological and physiological processes through various mechanisms. However, the signature of lncRNA expression and the possible roles of lncRNAs in spinal cord injury (SCI) rat neurogenic bladder (NB) have not been comprehensively explored. In this study, the expression profiles of lncRNAs and mRNAs were explored in the bladder tissue of SCI rats using next-generation sequencing (NGS).MethodsTwenty female Wistar rats were randomly divided into SCI 1–3 and normal control (NC) groups. The spinal cord was completely transected at the T9–T10 level to establish the SCI model. Bladder tissues were collected on days 7, 14, and 28 after the operation. The expression profiles of lncRNAs were detected by NGS. Differentially expressed lncRNAs (DELs) were chosen for qRT-PCR verification to validate the RNA sequencing results. The functions of the predicted target genes were then evaluated using Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.ResultsCompared with the NC group, the SCI 1–3 groups had 468, 117, and 408 DELs [fold change (FC) >2], including 247, 38, and 201 up-regulated and 163, 79, and 207 down-regulated lncRNAs, respectively. Likewise, 6,654, 2,133, and 5,706 mRNAs (FC >2) were differentially expressed between SCI 1–3 and NC rats, of which 4,821, 1,195, and 3,695 were up-regulated, and 1,833, 938, and 2,011 were down-regulated, respectively. Specifically, Miat, Mir155hg, and H19 were significant DELs in all SCI groups. Moreover, GO revealed that the DELs were related to several terms, including immune response, and KEGG was mainly enriched in 10 pathways, such as the transforming growth factor β signaling pathway.ConclusionsThe results revealed the expression profiles and possible roles of lncRNAs in SCI rat NB. This study may help identify possible NB mechanisms following SCI from the perspective of lncRNAs and provides new potential lncRNAs for the early diagnosis and treatment of human NB in the future.

A prognostic signature based on the expression profile of the ferroptosis-related long non-coding RNAs in hepatocellular carcinoma.

Ferroptosis is a special form of cell death with extensive biological associations with various cancers; however, the role of aberrantly expressed ferroptosis-related long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) remains unclear. To explore the role and prognostic value of ferroptosis-related lncRNAs in HCC and to screen potential therapeutic targets. The RNA-seq data for 424 HCC patients and clinical data for 377 HCC patients were obtained from The Cancer Genome Atlas (TCGA) and evaluated using the Pearson's test to identify differentially expressed lncRNAs. The univariate analysis, least absolute shrinkage and selection operator Cox regression analysis were performed to construct and validate a prognostic risk-score model. The prognostic capacity was evaluated using the Kaplan-Meier method, univariate and multivariate Cox regression, and receiver operating characteristic (ROC) curve analyses. The enrichment analysis was performed to explore the functions of ferroptosis-related lncRNAs from the perspective of tumor immunology. Seventeen differentially expressed lncRNAs were identified (AL139384.1, AL928654.1, MKLN1-AS, AC145207.8, LINC00205, ZFPM2-AS1, LINC00942, POLH-AS1, AC090772.3, AL603839.3, AC012073.1, AC099850.1, AC026401.3, AP001469.3, AL031985.3, SNHG10, SNHG21) to establish the risk-score model. Survival analyses demonstrated poorer survival in high-risk patients, and the risk score was shown to be a better independent prognostic factor than conventional clinical characteristics. Additionally, we found close correlations between the risk score and immune cell subpopulation functions, as well as between the expression of immune checkpoint and carcinogenic N6-methyladenosine (m6A)-related mRNAs. The novel ferroptosis-related lncRNA signature may serve as an individualized prognostic prediction tool for patients with HCC.

Expression profiling of cancer-related long non-coding RNAs revealed upregulation and biomarker potential of HAR1B and JPX in colorectal cancer.

Aberrant expressions of long non-coding RNAs promote cancer development including colorectal cancer. Expression profiling of cancer-related lncRNAs may introduce new deregulated lncRNAs that might be recruited as novel platforms in diagnosis and therapy of CRC. In this study, we exploited the SBI Human LncProfiler qPCR Array to examine the expression pattern of 90 cancer-related lncRNAs in CRC samples. Among deregulated lncRNAs, HAR1B, JPX, and KRASP1- which were showed a significantly higher expression profile in aggressive CRC tumors- were selected for more validation. We found that HAR1B and JPX expression profiles may discriminate between adjacent, adenomatous colorectal polyps, and colorectal cancer samples. The area under the curve of near 0.7 and a sensitivity/specificity of more than 70.80%, respectively, claim a suitable cancer prognostic potential for these two lncRNAs, JPX and HAR1B. Further analysis revealed that HAR1B and JPX may contribute to CRC pathobiology through affecting the FOXO, ErbB, and Wnt/β-catenin signaling pathways. Upregulated JPX and HAR1B lncRNAs may contribute to colorectal cancer pathobiology by affecting multiple cancer-related signaling pathways. They also potentially discriminate between CRC tumors, marginals, and adenomatous colorectal polyps.

Altered expression profile of long non-coding RNAs during heart aging in mice

Abstract Objective Long noncoding RNAs (lncRNAs) play an important role in regulating the occurrence and development of cardiovascular diseases. However, the role of lncRNAs in heart aging remains poorly understood. The objective of this study was to identify differentially expressed lncRNAs in the heart of aging mice and elucidate the relevant regulatory pathways of cardiac aging. Materials and methods Echocardiography was used to detect the cardiac function of 18-months (aged) and 3-months (young) old C57BL/6 mice. Microarray analysis was performed to unravel the expression profiles of lncRNAs and mRNAs, and qRT-PCR to verify the highly dysregulated lncRNAs. Results Our results demonstrated that the heart function in aged mice was impaired relative to young ones. Microarray results showed that 155 lncRNAs were upregulated and 37 were downregulated, and 170 mRNAs were significantly upregulated and 44 were remarkably downregulated in aging hearts. Gene ontology analysis indicated that differentially expressed genes are mainly related to immune function, cell proliferation, copper ion response, and cellular cation homeostasis. KEGG pathway analysis showed that the differentially expressed mRNAs are related to cytokine-cytokine receptor interaction, inflammatory mediator regulation of TRP channels, and the NF-kappa B signaling pathway. Conclusion These results imply that the differentially expressed lncRNAs may regulate the development of heart aging. This study provides a new perspective on the potential effects and mechanisms of lncRNAs in heart aging.

A prognostic signature based on the expression profile of the ferroptosis-related long non-coding RNAs in hepatocellular carcinoma

A prognostic signature based on the expression profile of the ferroptosis-related long non-coding RNAs in hepatocellular carcinoma

Effects of autophagy modulators tamoxifen and chloroquine on the expression profiles of long non-coding RNAs in MIAMI cells exposed to IFNγ

Mesenchymal stromal cells (MSCs) can be utilized clinically for treatment of conditions that result from excessive inflammation. In a pro-inflammatory environment, MSCs adopt an anti-inflammatory phenotype resulting in immunomodulation. A sub-type of MSCs referred to as “marrow-isolated adult multilineage inducible” (MIAMI) cells, which were isolated from bone marrow, were utilized to show that the addition of autophagy modulators, tamoxifen (TX) or chloroquine (CQ), can alter how MIAMI cells respond to IFNγ exposure in vitro resulting in an increased immunoregulatory capacity of the MIAMI cells. Molecularly, it was also shown that TX and CQ each alter both the levels of immunomodulatory genes and microRNAs which target such genes. However, the role of other non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs) in regulating the response of MSCs to inflammation has been poorly studied. Here, we utilized transcriptomics and data mining to analyze the putative roles of various differentially regulated lncRNAs in MIAMI cells exposed to IFNγ with (or without) TX or CQ. The aim of this study was to investigate how the addition of TX and CQ alters lncRNA levels and evaluate how such changes could alter previously observed TX- and CQ-driven changes to the immunomodulatory properties of MIAMI cells. Data analysis revealed 693 long intergenic non-coding RNAS (lincRNAs), 480 pseudogenes, and 642 antisense RNAs that were differentially regulated with IFNγ, IFNγ+TX and IFNγ+CQ treatments. Further analysis of these RNA species based on the existing literature data revealed 6 antisense RNAs, 2 pseudogenes, and 5 lincRNAs that have the potential to modulate MIAMI cell’s response to IFNγ treatment. Functional analysis of these genomic species based on current literature linking inflammatory response and ncRNAs indicated their potential for regulation of several key pro- and anti-inflammatory responses, including NFκB signaling, cytokine secretion and auto-immune responses. Overall, this work found potential involvement of multiple pro-and anti-inflammatory pathways and molecules in modulating MIAMI cells’ response to inflammation.

Analysis of competing endogenous RNA (ceRNA) crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most common chronic inflammatory diseases, and has various phenotypes. Although its pathophysiology remains obscure, evidence has shown that dysregulation of noncoding RNAs (ncRNAs) is associated with CRSwNP. ncRNAs in the cytoplasm can act as competing endogenous RNAs (ceRNAs), which are involved in many inflammatory processes. However, the ceRNA crosstalk in CRSwNP is still unclear METHODS: We investigated expression profiles of messenger RNA (mRNA), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) in eosinophilic CRSwNP and constructed a global triple ceRNA network. As a result, 964 differentially expressed mRNAs (DEmRs), 207 differentially expressed miRNAs (DEmiRs), and 15 differentially expressed lncRNAs (DElncRs) were identified, and a ceRNA network containing 598 miRNA-mRNA pairs and 70 lncRNA-miRNA pairs was finally constructed. Gene set enrichment analysis (GSEA) results indicated these DEmRs were mainly enriched in "cytokine-cytokine receptor interaction," "salivary secretion," "hematopoietic cell lineage," and "chemokine signaling pathway." Moreover, we also predicted the subcellular localization of the DElncRs identified in the network via bioinformatics approaches CONCLUSION: In summary, the present study provided the first comprehensive assessment of the ceRNA crosstalk in eosinophilic CRSwNP. These findings will be of interest to the understanding of the potential pathophysiology of this disease.

Insights Into Long Non-Coding RNA and mRNA Expression in the Jejunum of Lambs Challenged With Escherichia coli F17.

It has long been recognized that enterotoxigenic Escherichia coli (ETEC) is the major pathogen responsible for vomiting and diarrhea. E. coli F17, a main subtype of ETEC, is characterized by high morbidity and mortality in young livestock. However, the transcriptomic basis underlying E. coli F17 infection has not been fully understood. In the present study, RNA sequencing was conducted to explore the expression profiles of mRNAs and long non-coding RNAs (lncRNAs) in the jejunum of lambs who were identified as resistant or sensitive to E. coli F17 that was obtained in a challenge experiment. A total of 772 differentially expressed (DE) mRNAs and 190 DE lncRNAs were detected between the E. coli F17—resistance and E. coli F17-sensitive lambs (i.e., TFF2, LOC105606142, OLFM4, LYPD8, REG4, APOA4, TCONS_00223467, and TCONS_00241897). Then, a two-step machine learning approach (RX) combination Random Forest and Extreme Gradient Boosting were performed, which identified 16 mRNAs and 17 lncRNAs as potential biomarkers, within which PPP2R3A and TCONS_00182693 were prioritized as key biomarkers involved in E. coli F17 infection. Furthermore, functional enrichment analysis showed that peroxisome proliferator-activated receptor (PPAR) pathway was significantly enriched in response to E. coli F17 infection. Our finding will help to improve the knowledge of the mechanisms underlying E. coli F17 infection and may provide novel targets for future treatment of E. coli F17 infection.

Alteration of Ileal lncRNAs After Duodenal-Jejunal Bypass Is Associated With Regulation of Lipid and Amino Acid Metabolism.

Metabolic and bariatric surgery (MBS) can generate a drastic shift of coding and noncoding RNA expression patterns in the gastrointestinal system, which triggers organ function remodeling and may induce type 2 diabetes (T2D) remission. Our previous studies have demonstrated that the altered expression profiles of duodenal and jejunal long noncoding RNAs (lncRNAs) after the duodenal–jejunal bypass (DJB), an investigational procedure and research tool of MBS, can improve glycemic control by modulating the entero-pancreatic axis and gut–brain axis, respectively. As an indiscerptible part of the intestine, the ileal lncRNA expression signatures after DJB and the critical pathways associated with postoperative correction of the impaired metabolism need to be investigated too. High-fat diet-induced diabetic mice were randomly assigned into two groups receiving either DJB or sham surgery. Compared to the sham group, 1,425 dysregulated ileal lncRNAs and 552 co-expressed mRNAs were identified in the DJB group. Bioinformatics analysis of the differently expressed mRNAs and predicted target genes or transcriptional factors indicated that the dysregulated ileal lncRNAs were associated with lipid and amino acid metabolism-related pathways. Moreover, a series of lncRNAs and their potential target mRNAs, especially NONMMUT040618, Pxmp4, Pnpla3, and Car5a, were identified on the pathway. In conclusion, DJB can induce remarkable alteration of ileal lncRNA and mRNA expression. The role of the ileum in DJB tends to re-establish the energy homeostasis by regulating the lipid and amino acid metabolism.

A study on the roles of long non-coding RNA and circular RNA in the pulmonary injuries induced by polystyrene microplastics

Microplastics (MPs) pollution has become a global concern due to its close relation to the environment and human health. Recently, more and more studies have pointed out the existence of MPs in the air, but its potential inhalation toxicity is unclear. Polystyrene Microplastics (PS-MPs) is one of the representative MPs. Besides, non-coding RNA plays crucial roles in regulating gene expression. Therefore, this study aims to provide new insights into the molecular exploration of PS-MPs inhalation. In this study, Sprague Dawley（SD）rats were treated with 100 nm, 500 nm, 1 μm and 2.5 μm PS-MPs for three days. And then intra-tracheal instillation of saline or 100 nm PS-MPs with 0, 0.5, 1 and 2 mg/200 μL were performed in SD rats every two days for two consecutive weeks. The deposition of PS-MPs was observed through immunofluorescence. Lung histological alternations were observed in haematoxylin and eosin (H&E) staining sections. The expressions of pro-inflammatory cytokines were quantified by ELISA and qPCR. Genome-wide transcriptomic profiling of long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) in rats lung were done by ribosomal RNA depleted RNA sequencing and verified by qRT-PCR. We observed that 100 nm and 1 μm PS-MPs could deposite in the lungs. In addition, pathological examination shows alveolar destruction and bronchial epithelium arranged in a mess in PS-MPs groups. Furthermore, the expressions of pro-inflammatory cytokines IL-6, TNF-α and IL-1β were upregulated in PS-MPs exposed rats. Sequencing results showed that 269 circRNAs and 109 lncRNAs were differentially expressed in lung tissue of the saline and PS-MPs exposed rats. The upregulated expressions of lncRNA XLOC_031479, circRNA 014924 and circRNA 006603 and the downregulated expressions of lncRNA XLOC_014188 and circ003982 were identified by qRT-PCR in MPs group. The identified novel circRNAs and lncRNAs may paly important role in the development of lung inflammation caused by PS-MPs.

Integrated Transcriptome Analysis of Iris Tissues in Experimental Autoimmune Uveitis.

Uveitis is a severe ocular inflammatory disease that affects the uvea and frequently results in visual impairment, even irreversible blindness. The current treatments for uveitis have exhibited adverse side effects. To find novel targets of this disease, we perform comparative transcriptome analysis using normal (n = 4) and experimental autoimmune uveitis (EAU) (n = 4) rat iris samples. We mainly focus on the expression profiles of mRNAs and long non-coding RNAs, and identify NOD-like receptor signaling pathway as the one that plays a key role in the pathological changes of the EAU irises. Our work demonstrates that the EAU iris transcriptome can be mined to uncover novel targetable pathways for uveitis. The molecules in NOD-like receptor signaling pathway could be novel therapeutic targets for autoimmune uveitis.