H19- and hsa-miR-338-3p-mediated NRP1 expression is an independent predictor of poor prognosis in glioblastoma.
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ABSTRACT:
SUBMITTER: Liu Y
PROVIDER: S-EPMC8629300 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Gliomas are the most common primary brain tumors. Because of their high degree of malignancy, patient survival rates are unsatisfactory. Therefore, exploring glioma biomarkers will play a key role in early diagnosis, guiding treatment, and monitoring the prognosis of gliomas. We found two lncRNAs, six miRNAs, and nine mRNAs that were differentially expressed by analyzing genomic data of glioma patients. The diagnostic value of mRNA expression levels in gliomas was determined by receiver operating characteristic (ROC) curve analysis. Among the nine mRNAs, the area under the ROC curve values of only CEP55 and SHCBP1 were >0.7, specifically 0.834 and 0.816, respectively. Additionally, CEP55 and SHCBP1 were highly expressed in glioma specimens and showed increased expression according to the glioma grade, and outcomes of high expression patients were poor. CEP55 was enriched in the cell cycle, DNA replication, mismatch repair, and P53 signaling pathway. SHCBP1 was enriched in the cell cycle, DNA replication, ECM receptor interaction, and P53 signaling pathway. Age, grade, IDH status, chromosome 19/20 cogain, and SHCBP1 were independent factors for prognosis. Our findings suggest the PART1-hsa-miR-429-SHCBP1 regulatory network plays an important role in gliomas.
| S-EPMC7174919 | biostudies-literature
Project description:Disintegrin and metalloproteinase 12 (ADAM12) is thought to trigger the occurrence and development of numerous tumours, including colorectal, breast, and pancreatic cancers. On the basis of The Cancer Genome Atlas (TCGA) datasets, in this study, the relationship between ADAM12 gene expression and hepatocellular carcinoma (HCC), the prognostic value of this relationship, and the potential mechanisms influencing HCC development were evaluated. The results showed that the ADAM12 gene was significantly and highly expressed in liver cancer tissue. The high expression of the ADAM12 gene in liver cancer tissue significantly and positively correlated with T stage, pathological stage, and residual tumour. Kaplan-Meier and Cox regression analyses revealed that ADAM12 gene expression is an independent risk factor influencing the prognosis of patients with liver cancer. Pathway analyses of ADAM12 in HCC revealed ADAM12-correlated signalling pathways, and the expression level of ADAM12 was associated with immune cell infiltration. In vitro experiments demonstrated that the expression level of ADAM12 in Huh-7 and Hep3B cells was significantly higher than that in other HCC cells. ShRNA transfection experiments confirmed that the expression levels of TGF-β and Notch pathway-related proteins were significantly decreased. An EdU cell proliferation assay showed that a low level of ADAM12 gene expression significantly inhibited the proliferative activity of HCC cells. Cell cycle experiments showed that low ADAM12 expression blocked the G1/S phase transition. Overall, this research revealed that high ADAM12 gene expression implies a poor prognosis for patients with primary liver cancer. In addition, it is a potential indicator for the diagnosis of liver cancer.
| S-EPMC9033838 | biostudies-literature
Project description:Neurogenesis is a highly-regulated process occurring in the dentate gyrus that has been linked to learning, memory, and antidepressant efficacy. MicroRNAs (miRNAs) have been previously shown to play an important role in the regulation of neuronal development and neurogenesis in the dentate gyrus via modulation of gene expression. However, this mode of regulation is both incompletely described in the literature thus far and highly multifactorial. In this study, we designed sensors and detected relative levels of expression of 10 different miRNAs and found miR-338-3p was most highly expressed in the dentate gyrus. Comparison of miR-338-3p expression with neuronal markers of maturity indicates miR-338-3p is expressed most highly in the mature neuron. We also designed a viral "sponge" to knock down in vivo expression of miR-338-3p. When miR-338-3p is knocked down, neurons sprout multiple primary dendrites that branch off of the soma in a disorganized manner, cellular proliferation is upregulated, and neoplasms form spontaneously in vivo. Additionally, miR-338-3p overexpression in glioblastoma cell lines slows their proliferation in vitro. Further, low miR-338-3p expression is associated with increased mortality and disease progression in patients with glioblastoma. These data identify miR-338-3p as a clinically relevant tumor suppressor in glioblastoma.
| S-EPMC5426787 | biostudies-literature
Project description:BackgroundHuman cell division cycle associated 8 (CDCA8) a key regulator of mitosis, has been described as a potential prognostic biomarker for a variety of cancers, such as breast, colon and lung cancers. We aimed to evaluate the potential role of CDCA8 expression in the prognosis of liver cancer by analysing data from The Cancer Genome Atlas (TCGA).MethodsThe Wilcoxon rank-sum test was used to compare the difference in CDCA8 expression between liver cancer tissues and matched normal tissues. Then, we applied logistic regression and the Wilcoxon rank-sum test to identify the association between CDCA8 expression and clinicopathologic characteristics. Cox regression and the Kaplan-Meier method were used to examine the clinicopathologic features correlated with overall survival (OS) in patients from the TCGA. Gene set enrichment analysis (GSEA) was performed to explore possible mechanisms of CDCA8 according to the TCGA dataset.ResultsCDCA8 expression was higher in liver cancer tissues than in matched normal tissues. Logistic regression and the Wilcoxon rank-sum test revealed that the increased level of CDCA8 expression in liver cancer tissues was notably related to T stage (OR = 1.64 for T1/2 vs. T3/4), clinical stage (OR = 1.66 for I/II vs. III/IV), histologic grade (OR = 6.71 for G1 vs. G4) and histological type (OR = 0.24 for cholangiocarcinoma [CHOL] vs. hepatocellular carcinoma [LIHC]) (all P-values < 0.05). Kaplan-Meier survival analysis indicated that high CDCA8 expression was related to a poor prognosis in liver cancer (P = 2.456 × 10-6). Univariate analysis showed that high CDCA8 expression was associated with poor OS in liver cancer patients, with a hazard ratio (HR) of 1.85 (95% confidence interval [CI]: 1.47-2.32; P = 1.16 × 10-7). Multivariate analysis showed that CDCA8 expression was independently correlated with OS (HR = 1.74; CI: 1.25-12.64; P = 1.27 × 10-5). GSEA revealed that the apoptosis, cell cycle, ErbB, MAPK, mTOR, Notch, p53 and TGF-β signaling pathways were differentially enriched in the CDCA8 high expression phenotype.ConclusionsHigh CDCA8 expression is a potential molecular predictor of a poor prognosis in liver cancer.
| S-EPMC7938604 | biostudies-literature
Project description:Background & aimsIntrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide with an increasing incidence and limited therapeutic options. Therefore, there is an urgent need to open the field to new concepts for identifying clinically relevant therapeutic targets and biomarkers. Here, we explored the role and the clinical relevance of circular RNA (circRNA) circLTBP2 in iCCA.MethodsTransforming growth factor β (TGFβ)-regulated circRNAs were identified by dedicated microarrays in human HuCC-T1 iCCA cell line, and their clinical relevance was evaluated in independent cohorts of patients. Gain and loss of function of circLTBP2 combined with functional tests was performed in vitro and in vivo in mice. RNA pulldown, microRNA sequencing, and RNA immunoprecipitation were performed to explore the sponging activity of circLTBP2.ResultsCircLTBP2 (has_circ_0032603) was identified as a novel TGFβ-induced circRNA in several cholangiocarcinoma cell lines. CircLTBP2 promotes tumour cell proliferation, migration, and resistance to gemcitabine-induced apoptosis in vitro and tumour growth in vivo. Mechanistically, circLTBP2 acts as a competitive RNA regulating notably the activity of the tumour suppressor microRNA miR-338-3p, leading to the overexpression of its pro-metastatic targets. The restoration of miR-338-3p levels in iCCA cells reversed the pro-tumourigenic effects driven by circLTBP2, including the resistance to gemcitabine-induced apoptosis. In addition, circLTBP2 expression predicted a reduced survival, as detected in not only tumour tissues but also serum extracellular vesicles isolated from patients with iCCA.ConclusionsCircLTBP2 is a novel effector of the pro-tumourigenic arm of TGFβ and a clinically relevant biomarker easily detected from liquid biopsies in iCCA.Impact and implicationsIntrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer with limited therapeutic options. Opening the field to new concepts is urgently needed to improve the survival of patients. Here, we evaluated the role and the clinical relevance of circular RNA. We report that TGFβ-induced circLTBP2 contributes to CCA carcinogenesis and may constitute a clinically relevant prognostic biomarker detected in liquid biopsies.
| S-EPMC10665948 | biostudies-literature
Project description:BackgroundMicroRNAs have been identified as major regulators and therapeutic targets of glioblastoma (GBM). It is thus meaningful to study the miRNAs differentially expressed (DE-miRNAs) in GBM.Materials and methodsWe performed a meta-analysis of previously published microarray data using the R-based "metaMA" package to identify DE-miRNAs.The biological processes of the DE-miRNAs were then analyzed using FunRich. KEGG pathways of the DE-miRNAs gene targets were analyzed by mirPath V.3. Luciferase activity assay was performed to validate that OXSM is a direct target of hsa-miR338-3p. Flow cytometry was used to detect the effects of miR-338-3p on GBM cell proliferation, apoptosis and cell cycle.ResultsDE-miRNAs in blood and brain tissue from GBM were identified. "Type I interferon signaling pathway" and "VEGF and VEGFR signaling network" were the most significantly enriched biological processes shared by all GBM types. In KEGG pathway analysis, DE-miRNAs both in blood and tissue show altered fatty acid biosynthesis. Further validation shows hsa-miR-338-3p regulates fatty acid metabolism by directly targeting OXSM gene. In addition, our data revealed an accelerated cell cycle and an anti-apoptotic role for OXSM in glioma cells, which has not been reported. Finally, we confirmed that hsa-miR-338-3p inhibitor antagonized the effect of downregulation of OXSM on cell cycle and apoptosis of GBM cells.ConclusionWe revealed that hsa-miR-338-3p, down-regulated in GBM, may affect the biogenesis and rapid proliferation of glioma cells by regulating the level of OXSM, providing new insights into understanding the pathogenesis of GBM and developing strategies to improve GBM prognosis.
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Project description:Objective: The overexpression of transcription factor Sine oculis homeobox 1 (SIX1) is discovered in various malignant tumors and has been known to be closely associated with tumorigenesis, progression and prognosis. This study aims to determine the role of SIX1 in endometrial cancer (EC). Methods: In this study, we analyzed the SIX1 expression profile and the correlation with the corresponding clinical characteristics of EC samples from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases. Wilcoxon signed-rank test was applied to analyze the difference between tumor group and control group. The potential biological processes or signaling pathways related to SIX1 activity in EC was also assessed. Results: The results showed that SIX1 was overexpressed in EC tissues compared to normal tissues (P=2.029e-15, P=6.25e-6). The SIX1 level was correlated with tumor grade (P=2.91e-4), peritoneal cytology (P=0.005), and the subsequent tumor surgery (P=1.169e-4). SIX1 expression was negatively associated with overall survival rate (P=4.241e-4, P=0.000241) and served as an independent factor that affected EC overall survival rate (P=0.005063), similar to other factors such as age, Figo stage, and tumor (T) stage. SIX1 participates in cancer pathogenesis through gene regulation that involves PI3K/AKT/MTOR signaling, mitotic spindle, G2M checkpoint, E2F targets, NOTCH signaling, glycolysis, cholesterol homeostasis, DNA repair and early estrogen response. Conclusions: Our data demonstrate that SIX1 is overexpressed in EC and associated with adverse clinicopathological outcomes, which can function as an independent factor for EC prognosis.
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Project description:ABCF1, a member of the ATP-binding cassette (ABC) transporter family, is involved in the malignant progression of tumors. However, the role of ABCF1 in bladder cancer is poorly understood. In our study, we explored the differential expression of ABCF1 in bladder cancer and normal bladder tissues based on bioinformatic analysis and immunohistochemical results. GSEA was performed to ascertain the potential related signaling pathways of ABCF1. The relationship between ABCF1 expression and bladder cancer progression was analyzed using the GSE13507 dataset. In addition, the differential expression of ABCF1 in the cell lines was verified by quantitative real-time polymerase chain reaction (qRT‒PCR) and Western blotting. ABCF1 was upregulated in bladder cancer, and the high expression of ABCF1 was closely related to sex (P = 0.00056), grade (P = 0.00049), T stage (P = 0.00007), and N stage (P = 0.0076). High expression of ABCF1 was correlated with poor overall survival in bladder cancer patients (P < 0.001). In addition, univariate and multivariate Cox regression analyses showed that high ABCF1 expression was an independent factor for poor prognosis in bladder cancer patients. Therefore, ABCF1 expression is closely related to the progression of bladder cancer and can be used as a potential indicator of poor prognosis and a therapeutic target for bladder cancer.
| S-EPMC10022215 | biostudies-literature
Project description:CD24 is a glycosyl-phosphatidyl-inositol linked glycoprotein expressed in a broad range of cell types including cancer cells. Although it is overexpressed in nearly 70% of human cancers, copy number variation of the CD24 locus has not been reported for any cancer. Here, we analyzed the genomics, transcriptomics, and clinical data of 1082 breast cancer (BRCA) samples and other cancer samples from the clinically annotated genomic database, The Cancer Genome Atlas (TCGA). The GISTIC2 method was applied to stratify the CD24 copy number, and Cox regression was performed to compare hazard ratio (HR) of CD24 overexpression, amplification and other traditional prognosis features for overall survival (OS). Our data demonstrated that CD24 amplification strongly correlated with its mRNA overexpression as well as TP53 mutant, cancer proliferation and metastasis features. In particular, CD24 amplification was enriched in basal-like subtype samples and associated with poor clinical outcome. Surprisingly, based on the univariate Cox regression analysis, CD24 overexpression (HR = 1.62, P = 0.010) and copy number amplification (HR = 1.79, P = 0.022) was more relevant to OS than TP53 mutant, mutation counts, diagnosis age, and BRCA subtypes. And based on multivariate survival analysis, CD24 amplification remained the most significant and independent predictor for worse OS (HR = 1.88, P = 0.015).
| S-EPMC6581687 | biostudies-literature
Project description:As a vital feature of the microenvironment, hypoxia, especially long-term hypoxia, is known to promote metastasis and lead to poor prognosis in solid tumors. Circular RNAs (circRNAs) participate in important processes of cell proliferation and metastasis in cancers. However, the contribution of circRNAs to metastasis under long-term hypoxia is obscure. In this study, we aim to explore specific functions of circHIPK3 in long-term hypoxia-promoting metastasis of gastric cancer (GC). The hypoxic resistant gastric cancer (HRGC) cell lines we established previously, which were tolerant to 2% O2 conditions, were used as the long-term hypoxia model. We found that circHIPK3 was upregulated by HIF-2α in HRGC cells, and circHIPK3 facilitated the migration and invasion ability of HRGC cells. Further investigation proved that circHIPK3 promoted metastasis of HRGC cells directly by interacting with miR-653-5p and miR-338-3p to relieve the suppression of neuropilin 1 (NRP1), resulting in the activation of downstream ERK and AKT pathways. Our study identified oncogene functions of circHIPK3 under a long-term hypoxic microenvironment and the possibility of using circHIPK3 as a potential biomarker of long-term hypoxia in GC. In conclusion, circHIPK3 could promote GC metastasis via the miR-653-5p/miR-338-3p-NRP1 axis under a long-term hypoxic microenvironment.
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