scholarly journals Comprehensive Profile Analysis of Differentially Expressed circRNAs in Glucose Deprivation-Induced Human Nucleus Pulposus Cell Degeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Hongze Chang ◽  
Hongzhang Wang ◽  
Xiaolong Yang ◽  
Kemin You ◽  
Mingwei Jiang ◽  
...  

Nucleus pulposus (NP) is the core substance to maintain the homeostasis of intervertebral disc and stability of biomechanics. The insufficient supply of nutrition (especially glucose) is an important factor that leads to the degeneration of NP cells. circRNAs play an important role in the process of intervertebral disc degeneration (IDD) by regulating the functions of NP cells. However, glucose deprivation-related circRNAs and their functions in IDD have not been reported. In this study, the differentially expressed circRNAs in NP cells after 0, 6, 12, and 24 h of glucose deprivation culture were detected by a microarray assay. Besides, time series clustering analysis by STEM software obtained the differentially up- and downregulated circRNAs during glucose deficiency. Then, the main functions and pathways of up- and downregulated circRNAs were predicted by the functional enrichment analysis. By constructing the circRNA-miRNA regulatory network, the potential mechanisms of the most differentially expressed circRNAs were predicted. In addition, according to in vitro validation, circ_0075062 was upregulated in degenerating NP tissues and glucose deprivation-induced NP cell degeneration. Based on Sanger sequencing and RNase tolerance assay, circ_0075062 was the circular transcript. Interfering with circ_0075062 expression could potentially alleviate the imbalance of extracellular matrix (ECM) synthesis and degradation in the NP cells induced by glucose deprivation. Together, these findings help us gain a comprehensive understanding of the underlying mechanisms of IDD, and circ_0075062 may be a promising therapeutic target of IDD.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Khaoula Errafii ◽  
Neyla S. Al-Akl ◽  
Olfa Khalifa ◽  
Abdelilah Arredouani

Abstract Background and aims The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as potential therapeutics. Here, we sought to identify the long non-coding RNAs (LncRNAs) associated with the steatosis improvement induced by the GLP-1R agonist Exendin-4 (Ex-4) in vitro. Methods Steatosis was induced in HepG2 cells with oleic acid. The transcriptomic profiling was performed using total RNA extracted from untreated, steatotic, and Ex-4-treated steatotic cells. We validated a subset of differentially expressed LncRNAs with qRT-PCR and identified the most significantly enriched cellular functions associated with the relevant LncRNAs. Results We confirm that Ex-4 improves steatosis in HepG2 cells. We found 379 and 180 differentially expressed LncRNAs between untreated and steatotic cells and between steatotic and Ex-4-treated steatotic cells, respectively. Interestingly, 22 upregulated LncRNAs in steatotic cells became downregulated with Ex-4 exposure, while 50 downregulated LncRNAs in steatotic cells became upregulated in the presence of Ex-4. Although some LncRNAs, such as MALAT1, H19, and NEAT1, were previously associated with NAFLD, the association of others with steatosis and the positive effect of Ex-4 is being reported for the first time. Functional enrichment analysis identified many critical pathways, including fatty acid and pyruvate metabolism, and insulin, PPAR, Wnt, TGF-β, mTOR, VEGF, NOD-like, and Toll-like receptors signaling pathways. Conclusion Our results suggest that LncRNAs may play essential roles in the mechanisms underlying steatosis improvement in response to GLP-1R agonists and warrant further functional studies.


2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.


2020 ◽  
Author(s):  
Gaochen Lan ◽  
Xiaoling Yu ◽  
Yanna Zhao ◽  
Jinjian Lan ◽  
Wan Li ◽  
...  

Abstract Background: Breast cancer is the most common malignant disease among women. At present, more and more attention has been paid to long non-coding RNAs (lncRNAs) in the field of breast cancer research. We aimed to investigate the expression profiles of lncRNAs and construct a prognostic lncRNA for predicting the overall survival (OS) of breast cancer.Methods: The expression profiles of lncRNAs and clinical data with breast cancer were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened out by R package (limma). The survival probability was estimated by the Kaplan‑Meier Test. The Cox Regression Model was performed for univariate and multivariate analysis. The risk score (RS) was established on the basis of the lncRNAs’ expression level (exp) multiplied regression coefficient (β) from the multivariate cox regression analysis with the following formula: RS=exp a1 * β a1 + exp a2 * β a2 +……+ exp an * β an. Functional enrichment analysis was performed by Metascape.Results: A total of 3404 differentially expressed lncRNAs were identified. Among them, CYTOR, MIR4458HG and MAPT-AS1 were significantly associated with the survival of breast cancer. Finally, The RS could predict OS of breast cancer (RS=exp CYTOR * β CYTOR + exp MIR4458HG * β MIR4458HG + exp MAPT-AS1 * β MAPT-AS1). Moreover, it was confirmed that the three-lncRNA signature could be an independent prognostic biomarker for breast cancer (HR=3.040, P=0.000).Conclusions: This study established a three-lncRNA signature, which might be a novel prognostic biomarker for breast cancer.


2021 ◽  
Author(s):  
Nana Yang ◽  
Qianghua Wang ◽  
Biao Ding ◽  
Yinging Gong ◽  
Yue Wu ◽  
...  

Abstract Background: The accumulation of ROS resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation likely plays important role in PE pathogenesis. This study aims to investigate expression profiles and functions of the ferroptosis-related genes (FRGs) in early- and late-onset preeclampsia.Methods: The gene expression data and clinical information were downloaded from GEO database. The “limma” R package was used for screening differentially expressed genes. GO(Gene Ontology), Kyoto Encyclopedia of Genes and Genomes(KEGG) and protein protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative real-time reverse transcriptase PCR was used to verify the expression of hub FRGs in PE.Results: A total number of 4,215 DEGs were identified between EOPE and preterm cases and 3,356 DEGs were found between EOPE and LOPE subtypes. 20 significantly different FRGs were identified in EOPE, while only 3 in LOPE. Functional enrichment analysis revealed that the differentially expressed FRGs was mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as response to hypoxia, iron homeostasis and iron ion binding process. The PPI network analysis and verification by RT-qPCR resulted in the identification of the following six interesting FRGs: FTH1, HIF1A, FTL, IREB2, MAPK8 and PLIN2. Conclusions: EOPE and LOPE owned distinct underlying molecular mechanisms and ferroptosis may be mainly implicated in pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.


Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 455 ◽  
Author(s):  
Qingyuan Ouyang ◽  
Shenqiang Hu ◽  
Guosong Wang ◽  
Jiwei Hu ◽  
Jiaman Zhang ◽  
...  

To date, research on poultry egg production performance has only been conducted within inter or intra-breed groups, while those combining both inter- and intra-breed groups are lacking. Egg production performance is known to differ markedly between Sichuan white goose (Anser cygnoides) and Landes goose (Anser anser). In order to understand the mechanism of egg production performance in geese, we undertook this study. Here, 18 ovarian stromal samples from both Sichuan white goose and Landes goose at the age of 145 days (3 individuals before egg production initiation for each breed) and 730 days (3 high- and low egg production individuals during non-laying periods for each breed) were collected to reveal the genome-wide expression profiles of ovarian mRNAs and lncRNAs between these two geese breeds at different physiological stages. Briefly, 58, 347, 797, 777, and 881 differentially expressed genes (DEGs) and 56, 24, 154, 105, and 224 differentially expressed long non-coding RNAs (DElncRNAs) were found in LLD vs. HLD (low egg production Landes goose vs. high egg production Landes goose), LSC vs. HSC (low egg production Sichuan White goose vs. high egg production Sichuan white goose), YLD vs. YSC (young Landes goose vs. young Sichuan white goose), HLD vs. HSC (high egg production Landes goose vs. high egg production Sichuan white goose), and LLD vs. LSC (low egg production Landes goose vs. low egg production Sichuan white goose) groups, respectively. Functional enrichment analysis of these DEGs and DElncRNAs suggest that the “neuroactive ligand–receptor interaction pathway” is crucial for egg production, and particularly, members of the 5-hydroxytryptamine receptor (HTR) family affect egg production by regulating ovarian metabolic function. Furthermore, the big differences in the secondary structures among HTR1F and HTR1B, HTR2B, and HTR7 may lead to their different expression patterns in goose ovaries of both inter- and intra-breed groups. These results provide novel insights into the mechanisms regulating poultry egg production performance.


Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 417
Author(s):  
Chuanxi Peng ◽  
Xing Wang ◽  
Tianyu Feng ◽  
Rui He ◽  
Mingcai Zhang ◽  
...  

MicroRNAs (miRNAs), the post-transcriptional gene regulators, are known to play an important role in plant development. The identification of differentially expressed miRNAs could better help us understand the post-transcriptional regulation that occurs during maize internode elongation. Accordingly, we compared the expression of MIRNAs between fixed internode and elongation internode samples and classified six differentially expressed MIRNAs as internode elongation-responsive miRNAs including zma-MIR160c, zma-MIR164b, zma-MIR164c, zma-MIR168a, zma-MIR396f, and zma-MIR398b, which target mRNAs supported by transcriptome sequencing. Functional enrichment analysis for predictive target genes showed that these miRNAs were involved in the development of internode elongation by regulating the genes respond to hormone signaling. To further reveal how miRNA affects internode elongation by affecting target genes, the miRNA–mRNA–PPI (protein and protein interaction) network was constructed to summarize the interaction of miRNAs and these target genes. Our results indicate that miRNAs regulate internode elongation in maize by targeting genes related to cell expansion, cell wall synthesis, transcription, and regulatory factors.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jun Ge ◽  
Quan Zhou ◽  
Junjie Niu ◽  
Yingjie Wang ◽  
Qi Yan ◽  
...  

Melatonin, a neuroendocrine hormone secreted by the pineal body, has a positive effect on intervertebral disc degeneration. The present study is aimed at investigating the biological role of melatonin in intervertebral disc degeneration and its underlying mechanism. A human nucleus pulposus cell (NPC) line was exposed to melatonin at different concentrations. Cell proliferation was measured by CCK-8 assay. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to measure the protein expression of indicated genes. A rabbit model of intervertebral disc degeneration was established to detect the role and mechanism of melatonin on intervertebral disc degeneration. Our study showed that melatonin promoted NPC viability and inhibited cell arrest. Furthermore, melatonin treatment led to the upregulation of collagen II and aggrecan and downregulation of collagen X. Moreover, melatonin significantly elevated the activity of the ERK signaling pathway. Inhibition of the ERK1/2 signals reversed the role of melatonin in the regulation of NPCs both in vitro and in vivo. Melatonin increased NPC viability through inhibition of cell cycle arrest and apoptosis. Moreover, melatonin promoted the secretion of functional factors influencing the nucleus pulposus cell physiology and retarded cell degeneration. Our results suggest that melatonin activated the ERK1/2 signaling pathway, thereby affecting the biological properties of the intervertebral disc degeneration.


2020 ◽  
Vol 9 (2) ◽  
pp. LMT30
Author(s):  
Chuanli Ren ◽  
Weixiu Sun ◽  
Xu Lian ◽  
Chongxu Han

Aim: To screen and identify key genes related to the development of smoking-induced lung adenocarcinoma (LUAD). Materials & methods: We obtained data from the GEO chip dataset GSE31210. The differentially expressed genes were screened by GEO2R. The protein interaction network of differentially expressed genes was constructed by STRING and Cytoscape. Finally, core genes were screened. The overall survival time of patients with the core genes was analyzed by Kaplan–Meier method. Gene ontology and Kyoto encyclopedia of genes and genomes bioaccumulation was calculated by DAVID. Results: Functional enrichment analysis indicated that nine key genes were actively involved in the biological process of smoking-related LUAD. Conclusion: 23 core genes and nine key genes among them were correlated with adverse prognosis of LUAD induced by smoking.


Genome ◽  
2017 ◽  
Vol 60 (12) ◽  
pp. 1021-1028 ◽  
Author(s):  
M.H. Ye ◽  
H. Bao ◽  
Y. Meng ◽  
L.L. Guan ◽  
P. Stothard ◽  
...  

While some research has looked into the host genetic response in pigs challenged with specific viruses or bacteria, few studies have explored the expression changes of transcripts in the peripheral blood of sick pigs that may be infected with multiple pathogens on farms. In this study, the architecture of the peripheral blood transcriptome of 64 Duroc sired commercial pigs, including 18 healthy animals at entry to a growing facility (set as a control) and 23 pairs of samples from healthy and sick pen mates, was generated using RNA-Seq technology. In total, 246 differentially expressed genes were identified to be specific to the sick animals. Functional enrichment analysis for those genes revealed that the over-represented gene ontology terms for the biological processes category were exclusively immune activity related. The cytokine–cytokine receptor interaction pathway was significantly enriched. Nine functional genes from this pathway encoding members (as well as their receptors) of the interleukins, chemokines, tumor necrosis factors, colony stimulating factors, activins, and interferons exhibited significant transcriptional alteration in sick animals. Our results suggest a subset of novel marker genes that may be useful candidate genes in the evaluation and prediction of health status in pigs under commercial production conditions.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Wenqing Nai ◽  
Diane Threapleton ◽  
Jingbo Lu ◽  
Kewei Zhang ◽  
Hongyuan Wu ◽  
...  

Abstract Atherosclerosis is the primary cause of cardiovascular events and its molecular mechanism urgently needs to be clarified. In our study, atheromatous plaques (ATH) and macroscopically intact tissue (MIT) sampled from 32 patients were compared and an integrated series of bioinformatic microarray analyses were used to identify altered genes and pathways. Our work showed 816 genes were differentially expressed between ATH and MIT, including 443 that were up-regulated and 373 that were down-regulated in ATH tissues. GO functional-enrichment analysis for differentially expressed genes (DEGs) indicated that genes related to the “immune response” and “muscle contraction” were altered in ATHs. KEGG pathway-enrichment analysis showed that up-regulated DEGs were significantly enriched in the “FcεRI-mediated signaling pathway”, while down-regulated genes were significantly enriched in the “transforming growth factor-β signaling pathway”. Protein-protein interaction network and module analysis demonstrated that VAV1, SYK, LYN and PTPN6 may play critical roles in the network. Additionally, similar observations were seen in a validation study where SYK, LYN and PTPN6 were markedly elevated in ATH. All in all, identification of these genes and pathways not only provides new insights into the pathogenesis of atherosclerosis, but may also aid in the development of prognostic and therapeutic biomarkers for advanced atheroma.


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