Cuproptosis-related ceRNA axis triggers cell proliferation and cell cycle through CBX2 in lung adenocarcinoma
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ABSTRACT:
SUBMITTER: Wu J
PROVIDER: S-EPMC10865584 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Cuproptosis is a novel form of programmed cell death. The role and mechanism of cuproptosis-related genes in prostate adenocarcinoma have not been fully understood. In this study, a series of bioinformatic analyses were performed. Consequently, glycine cleavage system protein H with high expression and unfavorable prognosis was regarded as the most potential cuproptosis-related gene in prostate adenocarcinoma. Moreover, glycine cleavage system protein H might be a promising indicator for predicting leuprolide sensitivity in prostate adenocarcinoma and three potential drugs targeting glycine cleavage system protein H were identified. Enrichment analysis revealed that glycine cleavage system protein H-correlated genes were significantly enriched in tricarboxylic acid cycle-related pathways. Subsequently, small nucleolar RNA host gene 17/miR-29a-3p axis was found to partially account for overexpression of glycine cleavage system protein H in prostate adenocarcinoma. Collectively, the current study elucidated a potential cuproptosis-related competing endogenous RNA axis small nucleolar RNA host gene 17/miR-29a-3p/glycine cleavage system protein H in prostate adenocarcinoma.
| S-EPMC10651496 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD) is the most ordinary histological subtype of lung cancer, and regulatory cell death is an attractive target for cancer therapy. Recent reports suggested that cuproptosis is a novel copper-dependent modulated form of cell death dependent on mitochondrial respiration. However, the role of cuproptosis-related genes (CRGs) in the LUAD process is unclear. In the current study, we found that DLD, LIAS, PDHB, DLAT and LIPA1 in 10 differentially expressed CRGs were central genes. GO and KEGG enrichment results showed that these 10 CRGs were mainly enriched in acetyl-CoA biosynthetic process, mitochondrial matrix, citrate cycle (TCA cycle) and pyruvate metabolism. Furthermore, we constructed a prognostic gene signature model based on the six prognostic CRGs, which demonstrated good predictive potential. Excitedly, we found that these six prognostic CRGs were significantly associated with most immune cell types, with DLD being the most significant (19 types). Significant correlations were noted between some prognostic CRGs and tumor mutation burden and microsatellite instability. Clinical correlation analysis showed that DLD was related to the pathological stage, T stage, and M stage of patients with LUAD. Lastly, we constructed the lncRNA UCA1/miR-1-3p/DLD axis that may play a key role in the progression of LUAD and screened nine active components of traditional Chinese medicine (TCM) that may regulate DLD. Further, in vitro cell experiments and molecular docking were used to verify this. In conclusion, we analyzed the potential value of CRGs in the progression of LUAD, constructed the potential regulatory axis of ceRNA, and obtained the targeted regulatory TCM active ingredients through comprehensive bioinformatics combined with experimental validation strategies. This work not only provides new insights into the treatment of LUAD but also includes a basis for the development of new immunotherapy drugs that target cuproptosis.
| S-EPMC9468865 | biostudies-literature
Project description:BackgroundLong non-coding RNA FOXD2 antisense RNA 1 (FOXD2-AS1) has been reported in many malignancies. However, the molecular mechanism of many actions is not clarified. This study was conducted to investigate the function of FOXD2-AS1 in lung adenocarcinoma and its molecular mechanism.MethodsBioinformatics and in vitro analysis including RT-qPCR, CFU, CCK8, Transwell, Cell Apoptosis and Cell Cycle Assay were used for the analysis of gene expression and related effects.ResultsIt revealed increased expression of lncRNA FOXD2-AS1 in lung adenocarcinoma cell lines (A549 cells), and abundant expression of lncRNA FOXD2-AS1 was also observed in the acquired lung adenocarcinoma tissues. In vitro results showed that knockdown of lncRNA FOXD2-AS1 in A549 cells weakened cell proliferation, invasion and increased apoptosis. At the same time, we found that reducing the expression of lncRNA FOXD2-AS1 caused cell cycle arrest in the G1/S phase. Differential gene analysis of lung adenocarcinoma and adjacent normal tissues showed that the cell cycle and its related process regulation were significantly enriched. Gene Set Enrichment Analysis (GSEA) analysis showed that miR-206, miR-143, lL6-JAK-STAT3 signalling pathway, STAT3, E2F targets, EZH2, P53 signalling pathway and E2F3 targets interacting with lncRNA FOXD2-AS1 were also enriched.ConclusionThis study demonstrates the role and mechanism of the lncRNA FOXD2-AS1 in lung adenocarcinoma and provides a better understanding for the treatment of lung adenocarcinoma, which indicates that interfering with lncRNA FOXD2-AS1 expression may be a novel strategy.
| S-EPMC9904230 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) is one of the most common cancers with high morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) serve as tumor promoters or suppressors in the development of various human malignancies, including LUAD. Although long intergenic non-protein coding RNA 1089 (LINC01089) suppresses the progression of breast cancer, its mechanism in LUAD requires further exploration. Thus, we aimed to investigate the underlying function and mechanism of LINC01089 in LUAD.MethodsThe expression of LINC01089 in LUAD and normal cell lines was detected. Functional assays were applied to measure cell proliferation, apoptosis and migration. Besides, mechanism experiments were employed for assessing the interplay among LINC01089, miR-301b-3p and StAR related lipid transfer domain containing 13 (STARD13). Data achieved in this study was statistically analyzed with Student's t test or one-way analysis of variance.ResultsLINC01089 expression was significantly down-regulated in LUAD tissues and cells and its overexpression could reduce cell proliferation and migration. Moreover, LINC01089 could regulate STARD13 expression through competitively binding to miR-301b-3p in LUAD. Additionally, rescue assays uncovered that STARD13 depletion or miR-301b-3p overexpression could countervail the restraining effect of LINC01089 knockdown on the phenotypes of LUAD cells.ConclusionLINC01089 served as a tumor-inhibitor in LUAD by targeting miR-301b-3p/STARD13 axis, providing an innovative insight into LUAD therapies. Trial registration Not applicable.
| S-EPMC8287768 | biostudies-literature
Project description:The disruption of epigenetic regulation is common in tumors; the abnormal expression of epigenetic factors leads to cancer occurrence and development. In this study, to investigate the potential function of histone methylation regulators in lung adenocarcinoma (LUAD), we performed differential expression analysis using RNA-seq data downloaded from The Cancer Genome Atlas (TCGA) database, and identified CBX2 and EZH2 as obviously upregulated histone methylation regulators. CBX2 knockdown significantly inhibited LUAD cell growth and metastasis in vitro and in vivo. The combined high expression of CBX2 and EZH2 was an indicator of poor prognosis in LUAD. The inhibition of both CBX2 and EZH2 exerted cooperative suppressive effects on the growth and metastasis of LUAD cells. Mechanistically, we revealed that CBX2 and EZH2 downregulated several PPAR signaling pathway genes and tumor suppressor genes through binding to their promoter cooperatively or separately. Furthermore, knockdown of CBX2 improved the therapeutic efficiency of EZH2 inhibitor on A549 cells. Our study reveals the cooperative oncogenic role of CBX2 and EZH2 in promoting LUAD progression, thereby providing potential targets for LUAD diagnosis and therapy.
| S-EPMC8760531 | biostudies-literature
Project description:Lung cancer is the most common tumor with severe morbidity and high mortality. Increasing evidence has demonstrated that SNX20 plays crucial roles in the progression of human cancer. However, the functions and mechanism of SNX20 in LUAD are still barely known. Here, we employ the TCGA, GEO and CCLE databases to examine the expression of SNX20 in human varies cancer, the results shown that SNX20 is down-regulated in lung Adenocarcinoma, SNX20 level was significantly positive correlated with poor prognosis and lung cancer immune cell infiltration. We found that over-expression of SNX20 significantly restrain NSCLC cell proliferation and migration. Subsequently, we discover a network regulating SNX20 in LUAD, further study found that the decreased of the SNX20 likely caused by DNA hypermethylation. Furthermore, we identified that SNX20AR/miRNA-301a-3p mediated decreased of SNX20 correlated with lung cancer progression and cancer immune infiltration in LUAD. Our findings suggested that ncRNAs play a crucial role in the regulatory network of SNX20. Collectively, our findings demonstrate the suppressor roles of the SNX20AR/miRNA-301a-3p/SNX20 axis in Lung Adenocarcinoma, represent that SNX20 have the potential of as an effective therapeutic target in future.
| S-EPMC8484765 | biostudies-literature
Project description:Previous studies have shown that long intergenic non-protein coding RNA 00518 (LINC00518) are essential for the cell growth and metastasis of human cancer. However, the role of LINC00518 in lung adenocarcinoma (LUAD) is still unknown. This research put emphasis on the function of LINC00518 on the cell growth of LUAD. The lncRNA, miRNA and mRNA expression were measured by using qRT-PCR. Protein levels were measured by using Western blotting. CCK-8, colony formation assays and transwell assay were performed to evaluate the cell proliferation ability and invasion. Bioinformatic analysis and luciferase reporter assays were chosen to confirm the mechanism of LINC00518 in LUAD. We found that LINC00518 was highly expressed in LUAD specimens and the high-expression was negatively correlated with the overall survival rates. This finding was also proved in the LUAD cell lines. Through a series of in vitro and in vivo experiments, we proved that LICN00518 promoted the cell growth of LUAD by regulating the cell cycle. Moreover, LICN00518 upregulated the expression of MECP2 by mutagenesis of miR-185-3p. The results suggested that LICN00518 could be used as a survival indicator and potential therapeutic target for LUAD patients.
| S-EPMC8081883 | biostudies-literature
Project description:IntroductionLong noncoding RNAs (lncRNAs) have been associated with many types of cancers, but their molecular mechanisms in lung squamous cell carcinoma (LUSC) have not been fully studied. Therefore, the current study investigated the regulation role of microRNA-205 host gene (MIR205HG) in LUSC and recognized the target genes managed by this lncRNA.MethodsMIR205HG expression was assessed by the quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The effects of silenced MIR205HG on cell biological behaviors were detected by colony formation assay, transwell assay, flow cytometry analysis and western blot analysis. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized to proof the binding relationship between miR-299-3p and MIR205HG/mitogen-activated protein kinase kinase kinase 2 (MAP 3 K2).ResultsThe expression levels of MIR205HG in LUSC tissues and cell lines were obviously up-regulated. Down-regulation of MIR205HG expression remarkably reduced cell proliferation, migration and epithelial-to-mesenchymal transition (EMT) progression, whereas promoted cell apoptosis. MIR205HG could bind with miR-299-3p and down-regulation of MIR205HG elevated miR-299-3p expression. MAP 3 K2 acted as the target gene of miR-299-3p and was up-regulated by MIR205HG overexpression. Overexpressing MAP 3 K2 could counteract the effects of down-regulating MIR205HG on LUSC progression to some degree.ConclusionMIR205HG acts as a competing endogenous RNA (ceRNA) to expedite cell proliferation and progression via targeting miR-299-3p in LUSC.
| S-EPMC7278044 | biostudies-literature
Project description:ObjectiveThis study aimed to describe the mechanism of exosome-derived miR-486-5p underlying the cell cycle and progression in lung adenocarcinoma (LUAD).MethodsBioinformatics methods were applied for identifying the differentially expressed genes (DEGs) in the GEO-LUAD dataset, predicting where the potential target miRNA was expressed and exploring the corresponding downstream target mRNA. qRT-PCR was conducted to detect the levels of the target genes in cancer cells. Thereafter, a series of in vitro experiments were performed for cell activities evaluation, including CCK-8, EdU, colony formation assay and transwell. Besides, Western blot was applied to determine the protein levels of the migration and invasion-related factors (NEK2, E-cadherin, N-cadherin, Vimentin, MMP-2, and MMP-9). Dual-luciferase reporter gene assay was employed for validating the targeted relationship between the target genes. Furthermore, nude mouse transplantation tumor experiment was conducted to further validate the role of the target miRNA in tumor development, and immunohistochemistry was used for Ki67 detection and TUNEL was applied for cell apoptosis assay.ResultsmiR-486-5p was observed to be enriched in serum exosomes, and seen to be significantly down-regulated in cancer tissues as well as in cancer serum exosomes. It was proven that exosomes could release miR-486-5p, thus regulating LUAD progression and affecting cell cycle. Moreover, NEK2 was identified as a target of miR-486-5p both in vivo and in vitro. Enrichment analysis revealed that NEK2 was mainly activated in cell cycle and mitosis-related pathways. Meanwhile, NEK2 was found to present significant difference in different TNM stages. Furthermore, rescue experiments indicated that the inhibitory effect of miR-486-5p overexpression on LUAD progression could be abrogated when miR-486-5p and NEK2 were simultaneously up-regulated.ConclusionExosome-derived miR-486-5p is responsible for cell cycle arrest as well as the inhibition of cell proliferation and metastasis in LUAD via targeting NEK2.
| S-EPMC7156548 | biostudies-literature
Project description:BackgroundsLung adenocarcinoma (LUAD) is the most common subtype of lung cancer, which is the leading cause of cancer death. Dysregulation of cell proliferation and death plays a crucial role in the development of LUAD. As of recently, the role of a new form of cell death, cuproptosis, and it has attracted more and more attention. As of yet, it is not clear whether cuproptosis is involved in the progression of LUAD.MethodsAn integrated set of bioinformatics tools was utilized to analyze the expression and prognostic significance of cuproptosis-related genes. Meanwhile, a robust risk signature was developed using machine learning based on prognostic cuproptosis-related genes and explored the value of prognostic cuproptosis-related signature for clinical applications, functional enrichment and immune landscape. Lastly, the dysregulation of the cuproptosis-related genes in LUAD was validated by in vitro experiment.ResultsIn this study, first, cuproptosis-related genes were found to be differentially expressed in LUAD patients of public databases, and nine of them had prognostic value. Next, a cuproptosis-related model with five features (DLTA, MTF1, GLS, PDHB and PDHA1) was constructed to separate the patients into high- and low-risk groups based on median risk score. Internal validation set and external validation set were used for model validation and evaluation. What's more, Enrichment analysis of differential genes and the WGCNA identified that cuproptosis-related signatures affected tumor prognosis by influencing tumor immunity. Small molecule compounds were predicted based on differential expressed genes to improve poor prognosis in the high-risk group and a nomogram was constructed to further advance clinical applications. In closing, our data showed that FDX1 affected the prognosis of lung cancer by altering the expression of cuproptosis-related signature.ConclusionA new cuproptosis-related signature for survival prediction was constructed and validated by machine learning algorithm and in vitro experiments to reflect tumor immune infiltration in LUAD patients. The purpose of this article was to provide a potential diagnostic and therapeutic strategy for LUAD.
| S-EPMC9811388 | biostudies-literature