SNX20AR/MiRNA-301a-3p/SNX20 Axis Associated With Cell Proliferation and Immune Infiltration in Lung Adenocarcinoma.
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SUBMITTER: Yuan Y
PROVIDER: S-EPMC8484765 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:PurposeFSTL3 expression is altered in various types of cancer. However, the role and mechanism of action of FSTL3 in lung adenocarcinoma development and tumor immunity are unknown. We investigated the association between FSTL3 expression and clinical characteristics and immune cell infiltration in lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) and a separate validation set from our hospital.MethodsData on immune system infiltration, gene expression, and relevant clinical information were obtained by analyzing lung adenocarcinoma sample data from TCGA database. Using online tools like GEPIA, the correlations between FSTL3 expression and prognosis, clinical stage, survival status, and tumor-infiltrating immune cells were examined. In a validation dataset, immunohistochemistry was performed to analyze FSTL3 expression and its related clinical characteristics.ResultsFSTL3 expression was markedly reduced in patients with lung adenocarcinoma. N stage, pathological stage, and overall survival were significantly correlated with FSTL3 expression. According to GSEA, FSTL3 is strongly linked to signaling pathways such as DNA replication and those involved in cell cycle regulation. Examination of TCGA database and TIMER online revealed a correlation between FSTL3 and B cell, T cell, NK cell, and neutrophil levels. The prognosis of patients with lung adenocarcinoma was significantly affected by six genes (KRT6A, VEGFC, KRT14, KRT17, SNORA12, and KRT81) related to FSTL3.ConclusionFSTL3 is significantly associated with the prognosis and progression of lung adenocarcinoma and the infiltration of immune cells. Thus, targeting FSTL3 and its associated genes in immunotherapy could be potentially beneficial for the treatment of lung adenocarcinoma.
| S-EPMC10799152 | biostudies-literature
Project description:Circular RNAs (circRNAs) are non‑coding RNAs that are connected at the 3' and 5' ends by an exon or intron. Studies increasingly show that circRNAs play an important role in tumorigenesis by acting as a 'sponge' for microRNAs (miRNAs), which abrogates the latter's effect on their target mRNAs. To identify a possible circRNA/miRNA/mRNA network in bladder cancer (BCa), we analyzed the circRNA and mRNA expression profiles of BCa and adjacent normal bladder tissues. A total of 127 circRNAs and 1,612 mRNAs were differentially expressed in the tumor tissues, and were primarily associated with cancer‑related pathways. A competing endogenous RNAs (ceRNA) network was then constructed which predicted a regulatory axis of circRNA_0071196, miRNA‑19b‑3p and its target gene citron Rho‑interacting serine/threonine kinase (CIT). Luciferase reporter assay validated the relationship between circRNA_0071196 and miRNA‑19b‑3p and of the latter with CIT. Furthermore, CIT was overexpressed in the BCa tissues, and was found to be correlated with metastasis and tumor histological grade. Knockdown of CIT in the human bladder cancer cell line 5367 significantly inhibited the proliferation, migration and colony formation capacity of the cells, and also upregulated the mediators of the p53 and RhoA‑ROCK signaling cascades that regulate cell cycle and migration. Taken together, our findings indicate that circRNA‑0071196 upregulates CIT levels in BCa by sponging off miRNA‑19b‑3p, and the circRNA_0071196/miRNA‑19b‑3p/CIT axis is a potential therapeutic target in BCa.
| S-EPMC7384843 | biostudies-literature
Project description:Background ZC3H12 family members have an important role in tumorigenesis and development. However, the relationship between ZC3H12 family members and the prognosis of lung adenocarcinoma (LUAD) and tumor infiltrating lymphocytes is not clear. Methods The expression of ZC3H12 family members in LUAD was analyzed by UALCAN. UALCAN, Kaplan–Meier Plotter, and GEPIA were used to evaluate the effect of ZC3H12 family members on the prognosis of LUAD. The relationship between prognostic ZC3H12 family members and 14 functional states of LUAD was studied by CancerSEA. The correlation between ZC3H12 and immune cell infiltration was studied by TIMMER. In addition, the correlation between ZC3H12D expression and an immune infiltration gene marker set was analyzed by TISIDB and GEPIA. Finally, the expression of ZC3H12D in LUAD was further verified by the GEO database and immunohistochemical staining. Results The combined prognostic analysis of UALCAN, Kaplan-Meier Plotter, and GEPIA showed that the up-regulated expression of ZC3H12D mRNA was closely related to an improvement in overall survival rate (OS) in patients with LUAD. There was no significant correlation between ZC3H12D and 14 functional states of LUAD. Further analysis showed that the expression of ZC3H12D was positively correlated with the infiltration of B cells and CD4+T cells in LUAD. The expression of ZC3H12D was also positively correlated with immune markers in LUAD, including B cell-derived TNF and LTA cytokines, CXCL13, and its receptor CXCR5. Immunohistochemical staining showed that the expression of ZC3H12D in LUAD tissue samples was higher than normal lung tissues. Conclusions These findings suggest that multiple ZC3H12 family members are associated with the prognosis of patients with LUAD tumors. The increased expression of ZC3H12D was correlated with improved prognosis. ZC3H12D was shown to be associated with the level of immune cell infiltration, including B cells and CD4+T cells. Thus, ZC3H12D can be used as a biomarker to judge the prognosis and immune infiltration of LUAD.
| S-EPMC8798865 | biostudies-literature
Project description:BackgroundLung adenocarcinoma (LUAD) is a common lung cancer with a poor prognosis under standard chemotherapy. Hypoxia is a crucial factor in the development of solid tumors, and hypoxia-related genes (HRGs) are closely associated with the proliferation of LUAD cells.MethodsIn this study, LUAD HRGs were screened, and bioinformatics analysis and experimental validation were conducted. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to gather LUAD RNA-seq data and accompanying clinical information. LUAD subtypes were identified by unsupervised cluster analysis, and immune infiltration analysis of subtypes was conducted by GSVA and ssGSEA. Cox regression and LASSO regression analyses were used to obtain prognosis-related HRGs. Prognostic analysis was used to evaluate HRGs. Differences in enrichment pathways and immunotherapy were observed between risk groups based on GSEA and the TIDE method. Finally, RT-PCR and in vitro experiments were used to confirm prognosis-related HRG expression in LUAD cells.ResultsTwo hypoxia-associated subtypes of LUAD were distinguished, demonstrating significant differences in prognostic analysis and immunological characteristics between subtypes. A prognostic model based on six HRGs (HK1, PDK3, PFKL, SLC2A1, STC1, and XPNPEP1) was developed for LUAD. HK1, SLC2A1, STC1, and XPNPEP1 were found to be risk factors for LUAD. PDK3 and PFKL were protective factors in LUAD patients.ConclusionThis study demonstrates the effect of hypoxia-associated genes on immune infiltration in LUAD and provides options for immunotherapy and therapeutic strategies in LUAD.
| S-EPMC10414028 | biostudies-literature
Project description:To identify the prognostic biomarker of the competitive endogenous RNA (ceRNA) and explore the tumor infiltrating immune cells (TIICs) which might be the potential prognostic factors in lung adenocarcinoma. In addition, we also try to explain the crosstalk between the ceRNA and TIICs to explore the molecular mechanisms involved in lung adenocarcinoma. The transcriptome data of lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database, and the hypergeometric correlation of the differently expressed miRNA-lncRNA and miRNA-mRNA were analyzed based on the starBase. In addition, the Kaplan-Meier survival and Cox regression model analysis were used to identify the prognostic ceRNA network and TIICs. Correlation analysis was performed to analysis the correlation between the ceRNA network and TIICs. In the differently expressed RNAs between tumor and normal tissue, a total of 190 miRNAs, 224 lncRNAs and 3024 mRNAs were detected, and the constructed ceRNA network contained 5 lncRNAs, 92 mRNAs and 10 miRNAs. Then, six prognostic RNAs (FKBP3, GPI, LOXL2, IL22RA1, GPR37, and has-miR-148a-3p) were viewed as the key members for constructing the prognostic prediction model in the ceRNA network, and three kinds of TIICs (Monocytes, Macrophages M1, activated mast cells) were identified to be significantly related with the prognosis in lung adenocarcinoma. Correlation analysis suggested that the FKBP3 was associated with Monocytes and Macrophages M1, and the GPI was obviously related with Monocytes and Macrophages M1. Besides, the LOXL2 was associated with Monocytes and Activated mast cells, and the IL22RA1 was significantly associated with Monocytes and Macrophages M1, while the GPR37 and Macrophages M1 was closely related. The constructed ceRNA network and identified Monocytes, Macrophages M1 and activated Mast cells are all prognostic factors for lung adenocarcinoma. Moreover, the crosstalk between the ceRNA network and TIICs might be a potential molecular mechanism involved.
| S-EPMC8155208 | biostudies-literature
Project description:Previous studies have indicated that lung adenocarcinoma (LUAD) is one of the common human malignancies, and its incidence keeps rising. With the help of microarray technology, downregulation of miR-373-3p was observed in LUAD tissues compared with normal lung tissues. Notably, the present study demonstrated that the expression of amyloid precursor protein (APP) mRNA in LUAD tissues was overexpressed compared with adjacent tissues. Bioinformatic analysis demonstrated that miR-373-3p may interact with the 3' untranslated region of APP mRNA, and then western blot and dual-luciferase reporter gene assays were employed to verify the interaction. Finally, CCK-8 assays were used to measure the tumor-suppressing effect of miR-373-3p on A549 and it was demonstrated that overexpression of miR-373-3p may more effectively inhibit the proliferation of A549 compared with APP si-RNA. Overall, the findings suggest that miR-373-3p downregulation partly accounts for APP overexpression and leads to a promotion of cell growth in LUAD. miR-373-3p may therefore act as a valuable target in potential anticancer strategies to treat LUAD.
| S-EPMC5768135 | biostudies-literature
Project description:BACKGROUND The exact mechanisms of lung adenocarcinoma (LUAD) etiology and pathogenesis remain unclear. MATERIAL AND METHODS In this study, we evaluated alternative splicing (AS) events in LUAD. We separately analyzed LUAD data from The Cancer Genome Atlas (TCGA) database and AS-related feature lists from SpliceSeq to develop risk models for AS events and further validated risk models for AS events. The association between immune-related features and the risk model of AS events was evaluated. RESULTS We found that exon skip (ES) and mutually exclusive exons (ME) exhibited the most and least AS events, respectively. The risk score and stage of LUAD patients were strongly associated with prognosis and were independent influences on the prognosis of LUAD. The pathological stage (stage, T, N) and risk model were incorporated to construct a column line graph with better predictive ability. Risk models were associated with tumor microenvironment, and higher risk score values were associated with higher M2 macrophage content and lower M0 macrophage and helper T lymphocyte content. The correlation between core genes and immunity was further assessed by analyzing differentially-expressed genes between risk models. These results suggest an association between the level of risk for AS events and the density of immune cell infiltration. CONCLUSIONS Our findings suggest a clear association between AS risk model and patient prognosis, and was performed to confirm the biological relationship between AS and immunity.
| S-EPMC8656114 | biostudies-literature
Project description:Janus kinase 1 (JAK1) is a member of the JAK family, which plays an essential and non-redundant role in tumorigenesis. However, the potential role of JAK1 in immune infiltration and prognosis of lung adenocarcinoma (LUAD) remains unclear. The mRNA expression and methylation level of JAK1 in LUAD were examined using the Oncomine and The Cancer Genome Atlas (TCGA) databases, respectively. The correlations between JAK1 expression and its methylation level and clinicopathological parameters were analyzed. The Kaplan-Meier plotter database was used to evaluate the prognostic value of JAK1 in LUAD. The signaling pathways associated with JAK1 expression were identified by performing a GSEA. The CIBERSORT and TIMER databases were used to analyze the correlations between JAK1 and tumor-infiltrating immune cells. In addition, the JAK1 expression and proportion of immune cells in LUAD cell lines were analyzed. The JAK1 expression was remarkably decreased in patients with LUAD and significantly correlated with the clinical features of patients with LUAD. The JAK1 methylation level was increased and negatively correlated with its mRNA expression. A decrease in JAK1 expression was correlated with poor prognosis. The results of GSEA showed that cell adhesion, tumorigenesis, and immune-related signaling pathways were mainly enriched. JAK1 was positively associated with tumor-infiltrating immune cells, and the results of CIBERSORT analysis suggested that JAK1 was correlated with monotypes and M1 macrophages. The results of the TIMER database analysis confirmed that JAK1 was closely associated with the gene markers of M1 macrophages. Thus, JAK1 may serve as a potential prognostic biomarker in LUAD and is associated with immune infiltration.
| S-EPMC7880401 | biostudies-literature
Project description:The neutrophils exhibit both anti-tumor and pro-tumor effects in cancers. The correlation between neutrophils and tumor development in lung adenocarcinoma (LUAD) is still uncertain, possibly due to a lack of specific neutrophil infiltration evaluation methods. In this study, we identified 30 hub genes that were significantly associated with neutrophil infiltration in LUAD through data mining, survival analysis, and multiple tumor-infiltrating immune cells (TICs) analysis, including TIMER, CIBERSORT, QUANTISEQ, XCELL, and MCPCOUNTER. Consensus clustering analysis showed that these 30 hub genes were correlated with clinical features in LUAD. We further developed a neutrophil scoring system based on these hub genes. The neutrophil score was significantly correlated with prognosis and tumor immune microenvironment (TIME) in LUAD. It was also positively associated with PD-L1 expression and negatively associated with tumor mutational burden (TMB). When combined with the neutrophil score, the predictive capacity of PD-L1 and TMB for prognosis was significantly improved. Thus, the 30 hub genes might play an essential role in the interaction of neutrophils and LUAD, and the neutrophil scoring system might effectually assess the infiltration of neutrophils. Furthermore, we verified the expression of these 30 genes in the LUAD tumor tissues collected from our department. We further found that overexpressed TNFAIP6 and TLR6 and downregulated P2RY13, SCARF1, DPEP2, PRAM1, CYP27A1, CFP, GPX3, and NCF1 in LUAD tissue might be potentially associated with neutrophils pro-tumor effects. The following in vitro experiments demonstrated that TNFAIP6 and TLR6 were significantly overexpressed, and P2RY13 and CYP27A1 were significantly downregulated in LUAD cell lines, compared to BEAS-2B cells. Knocking down TNFAIP6 in A549 and PC9 resulted in the upregulation of FAS, CCL3, and ICAM-1, and the downregulation of CCL2, CXCR4, and VEGF-A in neutrophils when co-culturing with the conditioned medium (CM) from LUAD cells. Knocking down TNFAIP6 in LUAD also led to an elevated early apoptosis rate of neutrophils. Therefore, overexpressed TNFAIP6 in LUAD cancer cells might lead to neutrophils "N2" polarization, which exhibited pro-tumor effects. Further research based on the genes identified in this pilot study might shed light on neutrophils' effects on LUAD in the future.
| S-EPMC10777728 | biostudies-literature