Gastric cancer is the fourth most frequent cancer and has a high death rate. Immunotherapy represented by PD-1 has brought hope for the treatment of advanced gastric cancer. Methylation of the m6A genes is linked to the onset and progression of numerous cancers, but there are few studies on gastric cancer. The main purpose of this study aims to analyze the relationship between m6A RNA methylation regulators, PD-L1, prognosis and tumor immune microenvironment (TIME) in gastric cancer. The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases were used to acquire transcriptomic data and clinical information from gastric cancer patients. The changes in m6A regulator expression levels in gastric cancer tissues and normal tissues were studied. Consensus clustering analysis was used to separate gastric cancer samples into two categories. We employed Least Absolute Shrinkage, Selection Operator (LASSO) Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and cBioPortal to analyze the m6A regulators, PD-L1 and TIME in gastric cancer. In gastric cancer tissues, the majority of m6A regulatory factors are considerably overexpressed. Two gastric cancer subgroups (Cluster1/2) based on consensus clustering of 21 m6A regulators. PD-L1 and PD-1 expression levels were significantly higher in gastric cancer tissues, and they were significantly linked with METTL3, WTAP, HNRNPD, ZC3H7B, METTL14, FTO, PCIF1, HNRNPC, YTHDF1 and YTDHF2. Cluster1 showed a large increase in resting memory CD4+ T cells, regulatory T cells, naïve B cells, active NK cells, and resting Mast cells. Cluster1 and Cluster2 were shown to be involved in numerous critical signaling pathways, including base excision repair, cell cycle, nucleotide excision repair, RNA degradation, and spliceosome pathways. Gastric cancer RiskScores based on prognostic factors have been found as independent prognostic indicators. The amount of tumor-infiltrating immune cells is dynamically affected by changes in the copy number of m6A methylation regulators associated with TIME.
BackgroundHepatocellular carcinoma (HCC) is a high-burden cancer. The molecular mechanism of HCC has not been fully elucidated. Notably, current research has revealed a significant function for long non-coding RNAs (lncRNAs) in the prognosis of patients with HCC. Here, this study aims to construct a regulated lncRNA-mediated ceRNA network and find biological targets for the treatment of HCC.MethodsBased on the RNA expression patterns from the TCGA, we did an analysis to determine which genes were expressed differently between liver tumor tissues and noncancerous tissues. Then, using bioinformatic tools, we built a lncRNA-miRNA-mRNA ceRNA network and used GO and KEGG functional analyses on the DEmRNAs connected to ceRNA networks. The main lncRNAs in the subnetwork were chosen, and we next looked at the relationships between these lncRNAs and the clinical characteristics of patients with HCC. The prognosis-related genes and immune cells were identified using Kaplan-Meier and Cox proportional hazard analyses, and CIBERSORT was utilized to separate the 22 immune cell types. CCK8 assay was performed to measure cell viability in HCC cells after lncRNA HOTTIP modulation.ResultsDifferentially expressed mRNA and lncRNAs in HCC and paracancerous tissues were identified. There are 245 lncRNAs, 126 miRNAs, and 1980 mRNAs that are expressed differently in liver tumour tissues than in noncancerous cells. Function analysis showed that mRNAs in ceRNA network were significantly enriched in G1/S transition of mototiv cell cycle, positive regulation of cell cycle process, hepatocellular carcinoma, and cancer related pathways. CD8 T cells and T follicular helper cells had a favourable link with a 0.65 correlation coefficient. Additionally, there was a strong correlation between Eosinophils, activated NK cells, and B memory cells. Strikingly, depletion of lncRNA HOTTIP inhibited viability of HCC cells. In addition, miR-205 upregulation suppressed viability of HCC cells, while miR-205 downregulation repressed viability of HCC cells. Notably, miR-205 depletion rescued HOTTIP depletion-mediated suppression of cell viability in HCC.ConclusionA ceRNA network was created by examining the lncRNA, miRNA, and mRNA expression profiles of liver tumours from the TCGA database. LncRNA HOTTIP promoted cell viability via inhibition of miR-205 in HCC cells.
Osteoarthritis is non-inflammatory degenerative joint arthritis, which exacerbates disability in elder persons. The molecular mechanisms of osteoarthritis are elusive. Ubiquitination, one type of post-translational modifications, has been demonstrated to accelerate or ameliorate the development and progression of osteoarthritis via targeting specific proteins for ubiquitination and determining protein stability and localization. Ubiquitination process can be reversed by a class of deubiquitinases via deubiquitination. In this review, we summarize the current knowledge regarding the multifaceted role of E3 ubiquitin ligases in the pathogenesis of osteoarthritis. We also describe the molecular insight of deubiquitinases into osteoarthritis processes. Moreover, we highlight the multiple compounds that target E3 ubiquitin ligases or deubiquitinases to influence osteoarthritis progression. We discuss the challenge and future perspectives via modulation of E3 ubiquitin ligases and deubiquitinases expression for enhancement of the therapeutic efficacy in osteoarthritis patients. We conclude that modulating ubiquitination and deubiquitination could alleviate the osteoarthritis pathogenesis to achieve the better treatment outcomes in osteoarthritis patients.
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