ZMYM3 May Promote Cell Proliferation in Small Cell Lung Carcinoma
Ontology highlight
ABSTRACT:
SUBMITTER: Kudo N
PROVIDER: S-EPMC8569135 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundLncRNA DLGAP1-AS2 plays an oncogenic role in glioma, while its role in other cancers is unknown. This study aimed to study the role of DLGAP1-AS2 in non-small cell lung cancer (NSCLC).MethodsExpression of DLGAP1-AS2 in NSCLC and paired non-tumor tissues from 64 NSCLC patients and the prognostic value of DLGAP1-AS2 for NSCLC were analyzed by performing a 5-year follow-up study. The interaction between DLGAP1-AS2 and miR-503 was confirmed by dual luciferase reporter assay, and their relationship was explored in NSCLC cells transfected with DLGAP1-AS2 expression vector or miR-503 mimic. The roles of DLGAP1-AS2 and miR-503 in regulating cyclin D1 expression were analyzed by RT-qPCR and Western blot. Cell proliferation was analyzed by CCK-8 assay.ResultsDLGAP1-AS2 was upregulated in NSCLC and predicted poor survival. Interaction between DLGAP1-AS2 and miR-503 was confirmed by dual luciferase activity assay. Overexpression experiments showed that DLGAP1-AS2 and miR-503 overexpression failed to significantly affect the expression of each other. Interestingly, DLGAP1-AS2 overexpression upregulated cyclin D1, a target of miR-503, increased cell proliferation and reduced the effects of miR-503 overexpression on cyclin D1 expression and cell proliferation.ConclusionsDLGAP1-AS2 may regulate miR-503/cyclin D1 to promote cell proliferation in NSCLC.
| S-EPMC8401159 | biostudies-literature
Project description:BackgroundThe latent involvement of MRPL13 in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to explore the role of MRPL13 in NSCLC.MethodsAll analyses were performed in R software 4.0, SPSS version 23, and GraphPad Prism 8. The "limma" package was used to identify differentially expressed genes. Univariate and multivariate cox analyses were used to identify prognosis-related genes. A549 and H1299 lung cancer cell lines were selected for phenotypic experiments.ResultsThe high level of MRPL13 was correlated with poor T classification and overall survival. In vitro experiments showed that MRPL13 was highly expressed in NSCLC tissue and cell lines. MRPL13 knockdown inhibited the proliferation of lung cancer A549 and H1299 cell lines, which was further validated by in vivo experiment. Moreover, GSEA analysis suggested that the pathway of MYC target, PI3K/AKT/mTOR/ signaling, oxidative phosphorylation, and G2/M checkpoints may be the potential pathway where MRPL13 was involved. Meanwhile, MRPL13 demonstrated a negative correlation with M1 macrophage, CD8+ T cells, and CD4+ T cells, making it an underlying immunotherapy target of NSCLC.ConclusionMRPL13 may promote the proliferation of NSCLC cells and serve as an independent tumor marker and an emerging therapeutic target.
| S-EPMC8285246 | biostudies-literature
Project description:Thrombopoietin (TPO) is a haematopoietic cytokine mainly produced by the liver and kidneys, which stimulates the production and maturation of megakaryocytes. In the past decade, numerous studies have investigated the effects of TPO outside the haematopoietic system; however, the role of TPO in the progression of solid cancer, particularly lung cancer, has not been well studied. Exogenous TPO does not affect non-small-cell lung cancer (NSCLC) cells as these cells show no or extremely low TPO receptor expression; therefore, in this study, we focused on endogenous TPO produced by NSCLC cells. Immunohistochemical analysis of 150 paired NSCLC and adjacent normal tissues indicated that TPO was highly expressed in NSCLC tissues and correlated with clinicopathological parameters including differentiation, P-TNM stage, lymph node metastasis and tumour size. Suppressing endogenous TPO by small interfering RNA inhibited the proliferation and migration of NSCLC cells. Moreover, TPO interacted with the EGFR protein and delayed ligand-induced EGFR degradation, thus enhancing EGFR signalling. Notably, overexpressing TPO in EGF-stimulated NSCLC cells facilitated cell proliferation and migration, whereas no obvious changes were observed without EGF stimulation. Our results suggest that endogenous TPO promotes tumorigenicity of NSCLC via regulating EGFR signalling and thus could be a therapeutic target for treating NSCLC.
| S-EPMC7299695 | biostudies-literature
Project description:MicroRNAs (miRNA) are a class of small, noncoding RNA molecules that regulate the expression of target genes. miRNA dysregulation is involved in carcinogenesis and tumor progression. In this study, we identified microRNA-1253 (miR-1253) as being significantly down-regulated in non-small-cell lung carcinoma (NSCLC) tissues and associated with advanced clinical stage, lymph node metastasis, and poor survival. The enhanced expression of miR-1253 significantly inhibited the proliferation, migration, and invasion of NSCLC cells in vitro. Bioinformatics analyses showed that miR-1253 directly targeted WNT5A (long isoform), which was confirmed using the dual-luciferase reporter assay. The inhibitory effects of miR-1253 on the growth and metastasis of NSCLC cells were attenuated and phenocopied by WNT5A (long) overexpression and knockdown, respectively. Consistent with the in vitro results, subcutaneous tumor and metastatic NSCLC mouse models showed that miR-1253 functions as a potent suppressor of NSCLC in vivo. Taken together, our findings indicated that miR-1253 inhibited the proliferation and metastasis of NSCLC cells by targeting WNT5A (long isoform) and provided new evidence of miR-1253 as a potential therapeutic target in NSCLC.
| S-EPMC5833797 | biostudies-literature
Project description:Interleukin-8 (IL-8/CXCL8) is a pro-angiogenic and pro-inflammatory chemokine that plays a role in cancer development. Non-small cell lung carcinoma (NSCLC) produces high amounts of IL-8, which is associated with poor prognosis and resistance to chemo-radio and immunotherapy. However, the signaling pathways that lead to IL-8 production in NSCLC are unresolved. Here, we show that expression and release of IL-8 are regulated autonomously by TRAIL death receptors in several squamous and adenocarcinoma NSCLC cell lines. NSCLC constitutively secrete IL-8, which could be further enhanced by glucose withdrawal or by treatment with TRAIL or TNFα. In A549 cells, constitutive and inducible IL-8 production was dependent on NF-κB and MEK/ERK MAP Kinases. DR4 and DR5, known regulators of these signaling pathways, participated in constitutive and glucose deprivation-induced IL-8 secretion. These receptors were mainly located intracellularly. While DR4 signaled through the NF-κB pathway, DR4 and DR5 both regulated the ERK-MAPK and Akt pathways. FADD, caspase-8, RIPK1, and TRADD also regulated IL-8. Analysis of mRNA expression data from patients indicated that IL-8 transcripts correlated with TRAIL, DR4, and DR5 expression levels. Furthermore, TRAIL receptor expression levels also correlated with markers of angiogenesis and neutrophil infiltration in lung squamous carcinoma and adenocarcinoma. Collectively, these data suggest that TRAIL receptor signaling contributes to a pro-tumorigenic inflammatory signature associated with NSCLC.
| S-EPMC9755151 | biostudies-literature
Project description:MicroRNA-302a-5p (miR-302a-5p) has been implicated in several cancers; however, its role in human non-small cell lung carcinoma (NSCLC) remains unknown. In this study, we showed that miR-302a-5p is downregulated in NSCLC tissues and cell lines. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays showed that overexpression of a miR-302a-5p mimic suppressed NSCLC cell proliferation, which was confirmed by the results of a cell cycle assay. Overexpression of miR-302a-5p also reduced the migration and invasion of NSCLC cells. Additionally, miR-302a-5p overexpression significantly inhibited NSCLC growth and metastasis in a mouse xenograft model. With regard to the underlying mechanism, integrin α6 (ITGA6) mRNA was shown to be a novel target of miR-302a-5p, and overexpression of ITGA6 attenuated the inhibitory effects of miR-302a-5p on the proliferation and migration of NSCLC cells. In clinical NSCLC samples, miR-302a-5p expression was negatively correlated with ITGA6 expression, which was high in the samples. Collectively, these results indicate that miR-302a-5p acts as a tumor suppressor in NSCLC by directly targeting ITGA6 mRNA and may be useful as a theranostic biomarker of NSCLC.
| S-EPMC6684888 | biostudies-other
Project description:Overexpression of DTYMK is related with tumorigenesis and progression in several human tumors. However, the role of upregulated DTYMK in hepatocellular carcinoma (HCC) patients still remains unclear. In this study, the DTYMK expression in HCC tumors was evaluated in three GEO series (GSE14520, GSE54236, GSE63898), TCGA-LIHC, and ICGC-IRLR-JP cohorts. Survival analysis of DTYMK based on TCGA-LIHC and ICGC-LIRI-JP cohorts was conducted. We found that DTYMK was dramatically upregulated in tumor tissue compared with that in adjacent liver tissue. Kaplan-Meier analysis revealed that high expression of DTYMK in HCC patients' tumor tissue was significantly corresponded to worse overall survival (OS) (P < 0.05). Further analysis showed that overexpressing DTYMK led to poor relapse free survival (RFS) and disease-specific survival (DSS) (all P < 0.05). In conclusion, DTYMK is upregulated in tumors and correlated with poor prognosis in HCC patients. In our report, DTYMK is higher expression in HCC cancer tissue and cell line than tumor adjacent tissue and normal liver cell line. Knocking down DTYMK can inhabit tumor cell proliferation by interfering cell cycle, whereas overexpression of DTYMK can promote tumor cell proliferation. These findings indicate that upregulation of DTYMK enhances tumor growth and proliferation by promoting cell cycle.
| S-EPMC8489954 | biostudies-literature
Project description:Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer?associated mortality worldwide. In the present study, a novel molecular therapeutic target for lung cancer was investigated. The protein expression level of fidgetin?like 1 (FIGNL1) in human lung cancer tissues was determined and its potential functions in the H1299 and A549 lung cancer cell lines was subsequently studied. In addition, the protein expression level of FIGNL1 in 109 lung cancer samples and corresponding para?cancerous tissues was investigated, using immunohistochemical staining. RNA interference and overexpression of FIGNL1 was used to determine the role of FIGNL1 in regulating cell proliferation, and cDNA microarray analysis was performed to identify the potential regulatory pathways. Lastly, the potential role of FIGNL1 in regulating tumorigenesis in lungs and also the proliferation of lung cancer cells was investigated. Firstly, lung cancer tissues were found to express higher protein levels of FIGNL1 and was significantly associated with decreased cell proliferation, migration and invasion abilities, and enhanced cell death. Overexpression of FIGNL1 significantly promoted cell proliferation, including decreased arrest at the G1 phase of the cell cycle and apoptosis, as well as increased ability for fission and migration. These in vitro findings were consistent with the results of the cell?line derived xenografts in BALB/c nude mice, where tumor growth was decreased when injected with cells transfected with shFIGNL1. Collectively, these results provide suggest that FIGNL1 is involved in cell growth and tumorigenesis.
| S-EPMC7721085 | biostudies-literature
Project description:Coiled-coil domain containing (CCDC) family members enhance tumor cell proliferation, and high CCDC protein levels correlate with unfavorable prognoses. Limited research demonstrated that CCDC106 may promote the degradation of p53/TP53 protein and inhibit its transactivity. The present study demonstrated that CCDC106 expression correlates with advanced TNM stage (P = 0.008), positive regional lymph node metastasis (P < 0.001), and poor overall survival (P < 0.001) in 183 non-small cell lung cancer cases. A549 and H1299 cells were selected as representative of CCDC106-low and CCDC106-high expressing cell lines, respectively. CCDC106 overexpression promoted A549 cell proliferation and xenograft tumor growth in nude mice, while siRNA-mediated CCDC106 knockdown inhibited H1299 cell proliferation. CCDC106 promoted AKT phosphorylation and upregulated the cell cycle-regulating proteins Cyclin A2 and Cyclin B1. Cell proliferation promoted by CCDC106 via Cyclin A2 and Cyclin B1 was rescued by treatment with the AKT inhibitor, LY294002. Our studies revealed that CCDC106 is associated with non-small cell lung cancer progression and unfavorable prognosis. CCDC106 enhanced Cyclin A2 and Cyclin B1 expression and promoted A549 and H1299 cell proliferation, which depended on AKT signaling. These results suggest that CCDC106 may be a novel target for lung cancer treatment.
| S-EPMC5432287 | biostudies-literature
Project description:Background:LncRNA SNHG9 has been shown to be an oncogenic lncRNA in glioblastoma, while its role in other cancers is unknown. The aim of this study was to investigate the role of SNHG9 in non-small cell lung cancer (NSCLC). Methods:The differential expression of SNHG9 in NSCLC was first explored by analyzing the TCGA dataset, followed by measuring the expression levels of SNHG9 in paired NSCLC and non-tumor tissues by RT-qPCR. Expression of miR-21 was also determined by RT-qPCR. Correlations were analyzed by linear regression. The interaction between miR-21 and SNHG9 was detected using RNA pull-down. The expression relationship between SNHG9 and miR-21 was analyzed by SNHG9 or miR-21 overexpression experiments. The effects of overexpression of SNHG9 on the methylation of miR-21 were analyzed by methylation-specific PCR (MSP). Cell proliferation was evaluated by CCK-8 assay. Results:By analyzing the TCGA dataset, we observed downregulation of SNHG9 in NSCLC, which was confirmed by measuring the expression levels of SNHG9 in paired NSCLC tumor tissues and non-tumor tissues from NSCLC patients involved in this study. MiR-21 was upregulated in NSCLC tumor tissues and inversely correlated with SNHG9 in cancer tissues but not in non-tumor tissues. The interaction between SNHG9 and miR-21 was predicted by bioinformatic analyses, which was further verified by RNA pull-down. In NSCLC cells, overexpression of SNHG9 led to downregulated miR-21 and increased methylation of miR-21 gene. In contrast, miR-21 did not affect the expression of SNHG9. In addition, overexpression of SNHG9 attenuated the enhancing effects of miR-21 on NSCLC proliferation. Conclusion:SNHG9 might downregulate miR-21 through methylation to suppress cancer cell proliferation.
| S-EPMC7473986 | biostudies-literature