BackgroundLncRNA Gas5 is known to be a key control element during growth, differentiation and development in mammalian species. However, the role and function of Gas5 in growth plate chondrocytes has not been determined.MethodsThe overexpression and knockdown models of Gas5 and miR-21 in cells and animals were constructed. Cell survival was determined by MTT assay and flow cytometry. Animal biochemical indices were measured by enzyme-linked immunosorbent assay, hematoxylin/eosin staining, immunohistochemistry or in situ hybridisation. Dual luciferase reporter gene assay was carried out to study targeting.ResultsFirst, we found the expression levels of fibroblast growth factor 1(FGF1) were up-regulated and miR-21 were down-regulated in Gas5 overexpressing model cells. Meanwhile, the expression levels of FGF1 and Gas5 were up-regulated in miR-21 knockdown model cells. Furthermore, cell proliferation was significantly promoted after Gas5 knockdown or miR-21 overexpression. Subsequently, Gas5 promoted apoptosis, while miR-21 suppressed apoptosis. Animal assays demonstrated that both Gas5 and dexamethasone suppressed proliferation and promoted apoptosis of growth plate chondrocytes, up-regulated FGF1 expression but reduced miR-21 expression. Finally, there was a binding relationship between Gas5, miR-21 and FGF1.ConclusionWe concluded that Gas5 regulated proliferation and apoptosis in growth plate by controlling FGF1 expression via miR-21 regulation.Electronic supplementary materialThe online version of this article (10.1186/s12929-018-0424-6) contains supplementary material, which is available to authorized users.
BackgroundThe activator protein (AP)-2α is involved in a wide variety of biologic processes in tumor. However, little is known about the role of AP-2α in human papillary thyroid carcinoma (PTC).MethodsThe immunohistochemical method was used to detect AP-2α expression in 63 PTC cases. Western blotting was carried out to assess the change in expression of certain proteins. The bioinformatics analysis of 496 PTC samples comes from The Cancer Genome Atlas (TCGA). The Gene Set Enrichment Analysis (GSEA) was performed using TCGA data set. Cell transfection was used to induce related protein expression or to repress it by RNA interference procedures.ResultsOur results demonstrated that AP-2α expression was higher in tumor tissues than the corresponding adjacent nontumor tissues, the positive substances of AP-2α were observed mainly in the cytoplasm of PTC, and AP-2α was positively correlated with histologic type (P=0.026) of PTC patients. The high expression of AP-2α mRNA was associated significantly with tumor stages (P=0.011), histologic type (P=0.019), and independently predicted shorter overall survival (P=0.005) based on TCGA analysis. Patients with high AP-2α mRNA expression have shorter overall survival compared to those with low AP-2α mRNA expression, particularly in advanced tumor stages (III and IV) of PTC patients (P=0.011). Multivariate analysis suggested that AP-2α mRNA expression might be an independent prognostic indicator for the survival of patients with PTC (P=0.037). Moreover, the association between enhanced AP-2α expression and two pathways (notch signaling and focal adhesion) was revealed by GSEA, and then confirmed by cellular experiments.ConclusionTaken together, our findings suggest that AP-2α may be a potential prognostic molecular marker and therapeutic target for PTC patients.
IntroductionTransferrin receptor protein 1 (TFRC), an ananda molecule associated with ferroptosis, has been identified as affecting a wide spectrum of pathological processes in various cancers, but the prognostic value correlates with the tumor microenvironment of TFRC in lower-grade glioma (LGG) is still unclear.Materials and methodsClinical pathological information and gene expression data of patients with LGG come from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GTEx, Oncomine, UCSC Xena, and GEO databases. We then used various bioinformatics methods and mathematical models to analyze those data, aiming to investigate the clinical significance of TFRC in LGG and illustrate its association with tumor immunity. In addition, the molecular function and mechanisms of TFRC were revealed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Immunohistochemical experiments and single-cell analysis have been performed.ResultsTFRC expression was highly expressed in many tumors and showed a poor prognosis. Including gliomas, it was significantly associated with several poor clinical prognostic variables, tumor immune microenvironment, tumor mutational burden (TMB), m6a modification, and ferroptosis in LGG. TFRC as a key factor was further used to build a prediction nomogram. The C-index, calibration curve, and decision curve analysis showed the nomogram was clinically useful and calibration was accurate. At the same time, we also demonstrated that promoter hypomethylation of DNA upstream of TFRC could lead to high TFRC expression and poor overall survival. There is a significant correlation between TFRC and CD8 + T cell, macrophage cell infiltration, and several immune checkpoints, such as PD-L1(cd274), CTLA4, and PD1, suggesting a novel direction for future clinical application. Functional and molecular mechanism analysis showed an association of TFRC expression with immune-related pathways through GSEA, GO, and KEGG analysis. Finally, immunohistochemical experiments and single-cell analysis confirmed the expression of TFRC in glioma.ConclusionTFRC may be a potential prognostic biomarker and an immunotherapeutic target for glioma.
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