Current Issue : April-June Volume : 2023 Issue Number : 2 Articles : 6 Articles
We aimed to explore the mechanism of the linoleic acid metabolism in metabolic syndrome (MetS). RNA-seq data for 16 samples with or without MetS from the GSE145412 dataset were collected. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and gene differential expression analysis were performed. Expression data of differentially expressed genes (DEGs) involved in the linoleic acid metabolism pathway were mapped to the pathway by using Pathview for visualization. There were 19 and 10 differentially expressed biological processes in the disease group and healthy group, respectively. 9 KEGG pathways were differentially expressed in the disease group. Linoleic acid metabolism was the only differentially expressed pathway in the healthy group. TheGSVA enrichment score of the linoleic acid metabolism pathway in the disease group was markedly lower than that in the healthy group. The GSEA result showed that the linoleic acid metabolism pathway was significantly downregulated in the disease group. JMJD7-PLA2G4B, PLA2G1B, PLA2G2D, CYP2C8, and CYP2J2 involved in the pathway were significantly downregulated in the disease group. This study may provide novel insight into MetS from the point of linoleic acid metabolism dysregulation....
Background. Glioblastoma (GBM) is a highly prevalent brain tumor characterized by high rates of morbidity, recurrence, and mortality. While temozolomide (TMZ) is commonly used as a first-line treatment for this cancer, the emergence of TMZ resistance limits its utility.The long noncoding RNA HOXA-AS2 reportedly drives GBM progression, but whether it can influence therapeutic resistance to TMZ has yet to be established. Methods. HOXA-AS2 expression was analyzed in TMZ-resistant and sensitive GBM tissue samples and cell lines by qPCR. A siRNA-based approach was used to knock down HOXA-AS2 in GBM cells, after which TMZ resistance was tested. Bioinformatics approaches were used to predict miRNA binding targets of HOXA-AS2, after which a series of luciferase reporter assay and rescue experiments with appropriate miRNA inhibitor/mimic constructs were performed to validate these predictions and to clarify the ability of HOXA-AS2 to regulate chemoresistant activity. Results. TMZresistant GBM patients and cell lines exhibited increased HOXA-AS2 expression that was correlated with worse overall survival. Knocking down HOXA-AS2 increased the sensitivity of resistant GBM cells to TMZ. miR-302a-3p was identified as a HOXA-AS2 target confirmed through luciferase reporter assays and rescue experiments, and IGF1 was further identified as a confirmed miR- 302a-3p target. In addition, HOXA-AS2 knockdown resulted in a corresponding drop in IGF1 expression consistent with indirect regulation mediated by miR-302a-3p. Conclusion. In summary, these results highlight the role of HOXA-AS2 as a driver of TMZ resistance in GBM through its ability to regulate the miR-302a-3p/IGF1 signaling axis, highlighting this pathway as a promising target for the diagnosis, therapeutic sensitization, and/or treatment of affected patients....
Background: Transient receptor potential (TRP) channels have high permeability to Ca2+ ions because they are nonselective ion channels. TRP channels have been implicated in tumor onset and progression, proliferation, and migration in recent years. However, the prognostic value of genes related to TRP and their specific mechanism in pancreatic adenocarcinoma (PAAD) are yet to be understood. Methods: Public databases such as TCGA and GEO were used to retrieve data on gene expression and clinical information of patients with pancreatic adenocarcinoma for our study. ConsensusClusterPlus package was used for unsupervised clustering analysis. The microenvironment cell population (MCP)-counter approach was employed to measure the immune cells infiltration status. The Pearson correlation was performed to identify TRP-associated lncRNAs. Results: Initially, we separated PAAD patients into three clusters depending on TRP-related genes, and of the three clusters, cluster B showed the least immune cell infiltration, which was correlated with poor prognosis. Moreover, GSVA enrichment analysis further revealed that cluster A was subjected to a considerable enrichment in carcinogenic signaling pathways, whereas cluster C was enriched in immune-related pathways. Then, using TRP-associated lncRNAs as a starting point, we constructed a prognostic risk model for PAAD patients that could efficiently predict their prognosis. Further, GSEA revealed that cancer-related pathways, for instance, the cell cycle, p53 signaling pathway, etc. were considerably enriched in the high-risk group. In addition, we looked into the link between the prognostic model and the immunological microenvironment. Lower cytotoxic lymphocytes, NK cells, CD8 T cells, and endothelial cells infiltration were found to be associated with high risk using the MCP-counter algorithm. The expression of CD274, POLE2, MCM6, and LOXL2 was also found to be higher in the high-risk group. TMB was also considerably greater in high-risk individuals, indicating that immune checkpoint inhibitors (ICIs) therapy may benefit them more. Lastly, qRTPCR further confirmed the differential expression of these prognostic TRP-associated lncRNAs, indicating that these lncRNAs play an imperative role in PAAD tumorigenesis. Conclusion: TRP family genes may represent a new class of candidate molecular markers of the occurrence and progression of PAAD. Risk models based on TRP-associated lncRNAs could provide important new references for immunotargeted therapy of pancreatic adenocarcinoma....
Tetralogy of fallot (TOF) in the fetus is a typical congential heart disease that occurs during the early embryonic period, being characterized by the abnormal development of conus arteriosus. The early diagnosis and prevention of fetal TOF is very important and there is a great need for exploring the pathogenesis of it in clinic. In this study, there were three cases being detected with TOF by fetal echocardiogram and confirmed by autopsy. We characterize the difference of expression of lncRNAs and mRNAs through sequencing analysis of 3 pairs of myocardial tissues of fetal TOF and those of age-matched controls. Compared with normal group, there were 94 differentially expressed lncRNAs and 83 mRNA transcripts in TOF (P < 0.05). Correlation analysis between lncRNA and mRNA further showed that differentially expressed lncRNA can be linked to mRNAs, suggesting the potential regulator role of lncRNA in mRNA expression. Our data serve as a fundamental resource for understanding the disease etiology of TOF....
Cuprotosis is a novel cell death mechanism that can be explored to treat various tumors. A few studies on the role of cuprotosisrelated long noncoding RNA (lncRNA) in the development and prognosis of kidney renal clear cell carcinoma (KIRC) have been reported. We aimed to study the relationship between the prognosis of patients suffering from KIRC and lncRNAs associated with cuprotosis. The Cancer Genome Atlas (TCGA) database was analyzed, and the transcriptome data and clinical information on the patients with KIRC were obtained. The cuprotosis-related lncRNAs were identified by using Pearson correlation analysis, and the significant changes in the lncRNAs associated with KIRC were studied by conducting the T-test. The cuprotosis-related lncRNAs with KIRC prognostic values were identified by using the univariate Cox analysis, least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM) methods. A prognostic marker composed of three cuprotosis-related lncRNAs was identified following the multivariate regression analysis method. Patients with KIRC were divided into two groups based on the expression characteristics of three cuprotosis-related lncRNAs by using the K nearest neighbor (KNN) cluster analysis method. Significant differences in survival were observed between the two groups. In addition, the results obtained following the independent prognostic analysis of the risk score (RS) and clinical correlation revealed that the three cuprotosis-related lncRNA prognostic markers could accurately predict the prognosis of patients with KIRC. The results reported herein provide new insights into the pathogenesis of KIRC and the contribution of lncRNAs associated with cuprotosis. The results also helped identify a prognostic indicator that could potentially provide information for KIRC treatment....
Background. Psoriasis is an immune and inflammation-related skin disease. Triptolide with immunosuppressive and anti-inflammatory properties has been utilized for psoriasis treatment. However, the potential immunological mechanisms of triptolide have not been fully elucidated. Methods. Using an imiquimod (IMQ)-induced psoriatic mouse model, we detected the effects of triptolide on psoriasis-like lesions including scales, thickening, and erythema. Methyl thiazol tetrazolium (MTT) cytotoxicity assay was performed for evaluating the influence of triptolide on cell viability. Gene expression at mRNA and protein levels were examined by reverse transcription-quantitative polymerase chain reaction and Western blot analysis, respectively. The combination between microRNA-204-5p (miR-204-5p) and signal transduction and transcription activator-3 (STAT3) was confirmed by luciferase reporter assay. Enzyme-linked immunosorbent assay was conducted to examine interleukin (IL)-17 and interferon-c (IFN-c) levels using corresponding kits. Hematoxylin and eosin staining was used for the visualization of epidermal thickness. Flow cytometry analysis was employed for examining T helper (Th) 17 cells. Results. Triptolide ameliorated IMQ-induced psoriatic skin lesions manifested by the decreased psoriasis area and severity indexes (PASI) scores. Triptolide inhibited Th17cell differentiation from splenocytes. Additionally, triptolide elevated miR-204-5p expression, whereas it downregulated STAT3 expression levels both in vitro and in vivo. Moreover, miR-204-5p directly targeted STAT3 in HaCaTcells. Furthermore, triptolide repressed the expression of proinflammatory cytokines in IMQ-evoked psoriasis-like mice. Conclusion. Triptolide inhibits STAT3 phosphorylation via upregulating miR-204-5p and thus suppressing Th17 response in psoriasis....
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