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Background: Glioma, the most common brain tumor, is a heterogeneous group of glia-derived tumors, the majority of which have characteristics of diffuse infiltration and immunosuppression. The LGALS protein family is a large class of sugar-binding proteins. Among them, LGALS3 has been reported to promote tumor development and progression in some cancers. However, the clinical significance and biological functions of LGALS3 in glioma remain virtually unknown. The purpose of our research is to detect LGALS3 expression and its prognostic value in glioma and reveal the relationship between its expression and the clinico/molecular-pathological features of patients and immune cell infiltration. Methods: LGALS3 protein expression was examined by immunohistochemistry. The mRNA expression data of LGALS3 was downloaded and analyzed from TCGA and Rembrandt datasets. The association between LGALS3 and glioma clinically relevant diagnostic/molecular markers (IDH, 1p19q, ATRX, MGMT, and TERT) was examined using the Chi-Squared (χ2) test. The correlation between LGALS3 expression and the infiltration of multiple intra-tumoral immune cell types, including B cells (CD20), T cells (CD4 and CD8), macrophages (CD68), and M2 tumor-associated macrophages (CD163), was evaluated by Spearman correlation analysis. Kaplan-Meier analysis and the Cox regression analysis were applied to evaluate the prognostic value of LGALS3 in glioma. The log-rank test was used to evaluate Kaplan-Meier results for significance. Results: Out of all 304 glioma cases, LGALS3 protein was expressed in 125 glioma cases (41.1%, 125/304), with 69.2% (9/13) in WHO I, 9.8% (8/82) in WHO II, 34.2% (26/76) in WHO III, and 61.7% (82/133) in WHO IV. The expression of LGALS3 was correlated with patient age, WHO grade, PHH3 (mitosis), Ki67 index, IDH, 1p/19q codeletion, and TERT promoter status. LGALS3 was an independent poor prognostic marker in diffusely infiltrating gliomas and was positively correlated with immune cell infiltration, particularly CD163+ tumor-associated macrophages in the TCGA dataset, Rembrandt dataset, and our SYSUCC cohort (R = 0.419, 0.627, and 0.724). Conclusion: LGALS3 was highly expressed in pilocytic astrocytoma, GBM, and IDH wild-type LGG. It served as a poor prognostic marker in diffusely infiltrating gliomas. Based on its prognostic significance and strong correlation with CD163+ TAMs, it may act as an important therapeutic target for human glioma.
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HOX genes are transcription factors that control morphogenesis, organogenesis and differentiation. Increasing evidence suggests that HOX genes play a role in hepatocellular carcinoma (HCC) progression; however few studies have defined the functional roles and mechanisms of action. In the present study, we used siRNA and forced-expression in multiple cell lines to define the role of HOXA7 in the regulation of proliferation of HCC in vitro and in vivo. Knockdown of endogenous HOXA7 decreased the proliferation of HepG2 and QGY-7703 cells. These changes were not associated with significant changes in cyclin D1 and CDK4. However, downregulation of HOXA7 significantly reduced cyclin E1 and CDK2 protein levels. Conversely, overexpression of HOXA7 in QSG-7701 cells stimulated proliferation and increased cyclin E1 and CDK2 protein levels. Our results confirmed that HOXA7 promoted cell proliferation, and these changes were mediated by cyclin E1/CDK2. These observations contribute to our understanding of the important roles of HOXA7 in HCC development and progression and HOXA7 could be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC.
Assuntos
Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Proteínas Oncogênicas/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Células Hep G2 , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , TransfecçãoRESUMO
Traditional antibody production technology within non-mammalian cell expression systems has shown many unsatisfactory properties for the development of therapeutic antibodies. Nevertheless, mammalian cell display technology reaps the benefits of producing full-length all human antibodies. Together with the developed cytidine deaminase induced in vitro somatic hypermutation technology, mammalian cell display technology provides the opportunity to produce high affinity antibodies that might be ideal for therapeutic application. This review was concentrated on the development of the mammalian cell display technology as well as the activation-induced cytidine deaminase induced in vitro somatic hypermutation technology and their applications for the production of therapeutic antibodies.