scholarly journals Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Khaoula Errafii ◽  
Neyla S. Al-Akl ◽  
Olfa Khalifa ◽  
Abdelilah Arredouani
Keyword(s):  
Hepg2 Cells ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Alcoholic Fatty Liver ◽  
Critical Pathways ◽  
Hepatic Lipid Accumulation

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.

scholarly journals Identification of a prognostic long non-coding RNA signature in breast cancer

2020 ◽  
Author(s):  
Gaochen Lan ◽  
Xiaoling Yu ◽  
Yanna Zhao ◽  
Jinjian Lan ◽  
Wan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cox Regression Analysis

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.

scholarly journals Identifcation of The Ferroptosis-Related Gene Signature In Placenta of Patients With Early-Onset Preeclampsia

2021 ◽  
Author(s):  
Nana Yang ◽  
Qianghua Wang ◽  
Biao Ding ◽  
Yinging Gong ◽  
Yue Wu ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Late Onset ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Ppi Network ◽  
Network Analyses

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.

scholarly journals Comparative Transcriptome Analysis Suggests Key Roles for 5-Hydroxytryptamlne Receptors in Control of Goose Egg Production

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 455 ◽  
Author(s):  
Qingyuan Ouyang ◽  
Shenqiang Hu ◽  
Guosong Wang ◽  
Jiwei Hu ◽  
Jiaman Zhang ◽  
...  
Keyword(s):  
Egg Production ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Production Performance ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Anser Anser

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.

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 ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Enrichment Analysis ◽  
Nucleus Pulposus Cell ◽  
Glucose Deprivation ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cell Degeneration

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.

scholarly journals Identification and validation of a miRNA-based prognostic signature for cervical cancer through an integrated bioinformatics approach

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yumei Qi ◽  
Yo-Liang Lai ◽  
Pei-Chun Shen ◽  
Fang-Hsin Chen ◽  
Li-Jie Lin ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Poor Prognosis ◽  
Expression Profiles ◽  
Survival Rates ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Additive Effects

AbstractCervical cancer is the fourth most common cancer in women worldwide. Increasing evidence has shown that miRNAs are related to the progression of cervical cancer. However, the mechanisms that affect the prognosis of cancer are still largely unknown. In the present study, we sought to identify miRNAs associated with poor prognosis of patient with cervical cancer, as well as the possible mechanisms regulated by them. The miRNA expression profiles and relevant clinical information of patients with cervical cancer were obtained from The Cancer Genome Atlas (TCGA). The selection of prognostic miRNAs was carried out through an integrated bioinformatics approach. The most effective miRNAs with synergistic and additive effects were selected for validation through in vitro experiments. Three miRNAs (miR-216b-5p, miR-585-5p, and miR-7641) were identified as exhibiting good performance in predicting poor prognosis through additive effects analysis. The functional enrichment analysis suggested that not only pathways traditionally involved in cancer but also immune system pathways might be important in regulating the outcome of the disease. Our findings demonstrated that a synergistic combination of three miRNAs may be associated, through their regulation of specific pathways, with very poor survival rates for patients with cervical cancer.

scholarly journals Immunogenomic Landscape Analysis of Prognostic Immune-Related Genes in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Peng Qin ◽  
Mengyu Zhang ◽  
Xue Liu ◽  
Ziming Dong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Immune Related Genes

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. HBV infection is an important risk factor for the tumorigenesis of HCC, given that the inflammatory environment is closely related to morbidity and prognosis. Consequently, it is of urgent importance to explore the immunogenomic landscape to supplement the prognosis of HCC. The expression profiles of immune‐related genes (IRGs) were integrated with 377 HCC patients to generate differentially expressed IRGs based on the Cancer Genome Atlas (TCGA) dataset. These IRGs were evaluated and assessed in terms of their diagnostic and prognostic values. A total of 32 differentially expressed immune‐related genes resulted as significantly correlated with the overall survival of HCC patients. The Gene Ontology functional enrichment analysis revealed that these genes were actively involved in cytokine‐cytokine receptor interaction. A prognostic signature based on IRGs (HSPA4, PSME3, PSMD14, FABP6, ISG20L2, TRAF3, NDRG1, NRAS, CSPG5, and IL17D) stratified patients into high-risk versus low-risk groups in terms of overall survival and remained as an independent prognostic factor in multivariate analyses after adjusting for clinical and pathologic factors. Several IRGs (HSPA4, PSME3, PSMD14, FABP6, ISG20L2, TRAF3, NDRG1, NRAS, CSPG5, and IL17D) of clinical significance were screened in the present study, revealing that the proposed clinical-immune signature is a promising risk score for predicting the prognosis of HCC.

scholarly journals Fine mapping of goat polledness variant in six Chinese native breeds

2021 ◽  
Author(s):  
Yong Li ◽  
tao chen ◽  
Manman Yang ◽  
hu han ◽  
Dan Jiang ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Genome Wide Association Study ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Specific Element ◽  
A Genome

Background: The genetic mechanism of goat polledness has been studied for decades, but identifying causative variants and functional genes remains challenging. Results: Using a genome-wide association study (GWAS), we identified a significant striking locus for polledness in two different goat breeds. To reduce the linkage disequilibrium among variants for localizing causative variants in the finer region, we sequenced 79 goats from six Chinese native breeds (Jining Gray, Matou, Guizhou black, Yunnan black bone, Chaidamu, and Ujumqin) and identified 483.5 kb CNV (150,334,567-150,818,099) translocated into the previously identified 11.7 kb polled intersex syndrome region, which was consistent with previous research using intersex goat populations. Within the 483.5 kb CNV, a ~322 bp horn-specific element, similar to the superfamily of tRNA-derived families of SINEs, located at the first intron of the ERG gene was identified. The results of the GO enrichment analysis showed that the Horn-SINE element-associated genes were involved in both nervous system and head development. Finally, we used RNA sequencing to investigate gene expression profiles in the horn bud and skin tissues of horned and polled goats. We identified 1077 and 1222 differentially expressed genes between the horn bud and skin tissue in polled and horned goats, respectively. We also identified 367 differentially expressed genes in horn buds between polled and horned animals and found that the two CNV-related genes, ERG and FOXL2 were upregulated in the horn bud of polled goats. Gene functional enrichment analysis demonstrated that the downregulated genes in the horn bud of polled goats were enriched in skeletal system development, whereas the upregulated genes were significantly overexpressed in muscle tissue development.

scholarly journals Integrated Bioinformatic Analysis Revealed the Regulation of Angiogenesis by Tumor Cells in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Meisi Huo ◽  
Kangkang Yu ◽  
Yahui Zheng ◽  
Lu Liu ◽  
Hao Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Endothelial Cells ◽  
Tumor Cells ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality, metastasis accounts for most of the cases. Angiogenesis plays an important role in cancer metastasis, but how tumor cells affect the function of endothelial cells by dictating their miRNA expression remains largely unknown.Differentially expressed miRNAs (DEMs) were identified through dataset downloaded from the Gene Expression Omnibus (GEO) database and analyzed by GEO2R. We then use online tools to obtain potential targets of candidate microRNAs(miRNAs) and functional enrichment analysis，as well as the protein-protein interaction (PPI). Finally, the function of miR-302c-3p was validated through in vitro assay.In the current study, we found that HCC cells altered miRNAs expression profiles of human umbilical vein endothelial cells (HUVECs) and miR-302c-3p was the most downregulated miRNA in HUVECs when they were co-cultured with HCC-LM3 cells. Functional enrichment analysis of the candidate targets revealed that these genes were involved in epigenetic regulation of gene expression, in particular, histone methylation. In addition, PPI network demonstrated distinct roles of genes targeted by miR-302c-3p. Importantly, inhibition of angiogenesis, migration and permeability by the most downregulated miR-302c-3p in HUVECs was confirmed in vitro. These findings brought us novel insight into the regulation of angiogenesis by HCC cells and provided potential targets for the development of therapeutic strategies.

scholarly journals Identification of a prognostic long non-coding RNA signature in breast cancer

2020 ◽  
Author(s):  
Gaochen Lan ◽  
Xiaoling Yu ◽  
Yanna Zhao ◽  
Jinjian Lan ◽  
Wan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cox Regression Analysis

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.

Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Wrky Transcription Factor ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Callose Deposition ◽  
Significant Probability

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.

Sign in / Sign up

Export Citation Format

Share Document