Long non-coding RNA LINC00346 regulates proliferation and apoptosis by targeting miR-128-3p/SZRD1 axis in glioma.

OBJECTIVE: Long non-coding RNAs (lncRNAs) participate in multiple processes of malignant tumors, including glioma. In this study, we aimed to explore the effect of LINC00346 on glioma and its underlying mechanism. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to analyze the expression patterns and survival risk of LINC00346, miR-128-3p and SUZ RNA binding domain containing 1 (SZRD1) in glioma tissues. The binding sites were predicted by bioinformatic databases, and then, validated by Dual-Luciferase assay and RNA immunoprecipitation (RIP). qRT-PCR and Western blot were performed to evaluate the gene expression levels. CellTiter-Glo® and colony formation assays were used to detect the proliferation of glioma cells. Flow cytometric analysis was used to evaluate the apoptosis of glioma cells. The xenograft models were established to investigate the impact of LINC00346 on tumor growth in vivo. RESULTS: We found that both LINC00346 and SZRD1 expression were negatively related to the poor overall survival rate in glioma patients. However, miR-128-3p showed the opposite effect of survival outcomes. LINC00346 knockdown remarkably restrained cell proliferation both in vitro and in vivo, as well as inducing apoptosis by acting as a molecular sponge of miR-128-3p. Moreover, miR-128-3p bound to SZRD1 3'-UTR in a sequence-specific manner. In addition, LINC00346 knockdown significantly inhibited the expression of SZRD1 and the inhibition could be reversed by miR-128-3p mimics. Furthermore, cell proliferation and apoptosis affected by LINC00346 were partially rescued by modulating miR-128-3p or SZRD1 expression. CONCLUSIONS: LINC00346/miR-128-3p/SZRD1 axis played a crucial role in modulating the malignant progression of glioma, which may serve as a prognostic indicator and a probable therapeutic target for glioma.

Long non-coding RNA SNHG11 promotes cell proliferation, invasion and migration in glioma by targeting miR-154-5p.

OBJECTIVE: Long non-coding RNAs (lncRNAs) play critical roles in tumour progression. However, the function of lncRNA small nucleolar RNA host gene 11 (SNHG11) in glioma has not been mentioned before. Our study aims to uncover the biological roles of SNHG11 in the progression of glioma and throw light for clinical treatment of glioma. MATERIALS AND METHODS: The Gene Expression Profiling Interactive Analysis (GEPIA) dataset was used to analyze the SNHG11 expression between glioma and normal tissue, as well as survival benefit. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect SNHG11 and miR-154-5p expression. Celltiter-Glo, colony formation, and transwell assays were utilized to detect the influence of SNHG11 to the malignancy of U87 and U251 cells. The underlying pathways affected by SNHG11 were measured using Western blot. Furthermore, Luciferase reporter assay was applied to verify the interaction between SNHG11 and miR-154-5p. RESULTS: SNHG11 was upregulated in glioblastoma tissues and five malignant glioma cell lines. SNHG11 expression was negatively correlated with overall survival of glioma patients. Moreover, silencing of SNHG11 could decrease glioma cell viability both in vitro and in vivo. Furthermore, the inhibition of SNHG11 suppressed proliferation, invasion and migration via regulating epithelial-mesenchymal transition (EMT). In addition, SNHG11 could bind miRNA-154-5p and negatively regulate its level. CONCLUSIONS: SNHG11 functioned as an oncogene in glioma and promoted proliferation, invasion, and migration via EMT by sponging miR-154-5p. These findings provided a new therapeutic target for glioma.

CD1-restricted NK T cells protect nonobese diabetic mice from developing diabetes.

NK T cells are a unique subset of T cells that recognize lipid antigens presented by CD1d. After activation, NK T cells promptly produce large amounts of cytokines, which may modulate the upcoming immune responses. Previous studies have documented an association between decreased numbers of NK T cells and the progression of some autoimmune diseases, suggesting that NK T cells may control the development of autoimmune diseases. To investigate the role of NK T cells in autoimmune diabetes, we crossed CD1 knockout (CD1KO) mutation onto the nonobese diabetic (NOD) genetic background. We found that male CD1KO NOD mice exhibited significantly higher incidence and earlier onset of diabetes compared with the heterozygous controls. The diabetic frequencies in female mice showed a similar pattern; however, the differences were less profound between female CD1KO and control mice. Early treatment of NOD mice with alpha-galactosylceramide, a potent NK T cell activator, reduced the severity of autoimmune diabetes in a CD1-dependent manner. Our results not only suggest a protective role of CD1-restricted NK T cells in autoimmune diabetes but also reveal a causative link between the deficiency of NK T cells and the induction of insulin-dependent diabetes mellitus.