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RRM2 is a potential prognostic biomarker with functional significance in glioma.

ABSTRACT: Glioma is one of the most common brain tumors, suggesting the importance of investigating the molecular mechanism of gliomas. We studied the roles of Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in glioma. Expressions of RRM2 are higher in glioma tissues evidenced by TCGA data, western blot and immunohistochemistry. RRM2 is negatively correlated with glioma patient's survival. RNA-seq showed that genes involved in apoptosis, proliferation, cell adhesion and negative regulation of signaling were up-regulated upon RNAi-mediated knock-down of RRM2. Cell phenotypes specific for stably knocking down RRM2 were determined using stable transfection in vitro. In an in vivo model, knock-down of RRM2 inhibited tumor growth and caused suppression of AKT and ERK1/2 signalings. Interfering RRM2 also down-regulated the expression of cyclin A, cyclin B1, cyclin D1, Vimentin, and N-cadherin, and elevated E-cadherin expression. Moreover, overexpression of RRM2 failed to increase the expression of cyclin B1, cyclin D1, and N-cadherin when phosphorylation of AKT and ERK1/2 was suppressed by LY294002 or PD98059. These findings indicated that RRM2 is a positive regulator of glioma progression which contributes to the migration and proliferation of glioma cells through ERK1/2 and AKT signalings and might be a novel prognostic indicator for glioma patients.

SUBMITTER: Sun H

PROVIDER: S-EPMC6367584 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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RRM2 is a potential prognostic biomarker with functional significance in glioma.

Sun Hongzhi H Yang Bingya B Zhang Hao H Song Jingwei J Zhang Yenan Y Xing Jicheng J Yang Zhihui Z Wei Changyong C Xu Tuoye T Yu Zhennan Z Xu Zhipeng Z Hou Min M Ji Minjun M Zhang Yansong Y

International journal of biological sciences 20190101 3

Glioma is one of the most common brain tumors, suggesting the importance of investigating the molecular mechanism of gliomas. We studied the roles of Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in glioma. Expressions of RRM2 are higher in glioma tissues evidenced by TCGA data, western blot and immunohistochemistry. RRM2 is negatively correlated with glioma patient's survival. RNA-seq showed that genes involved in apoptosis, proliferation, cell adhesion and negative regulation of signal ...[more]

PMID: 30745840

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Project description:BackgroundTAP1 is an immunomodulation-related protein that plays different roles in various malignancies. This study investigated the transcriptional expression profile of TAP1 in uveal melanoma (UVM), revealed its potential biological interaction network, and determined its prognostic value.MethodsCIBERSORT and ESTIMATE bioinformatic methods were used on data sourced from The Cancer Genome Atlas database (TCGA) to determine the correlation between TAP1 expression, UVM prognosis, biological characteristics, and immune infiltration. Gene set enrichment analysis (GSEA) was used to discover the signaling pathways associated with TAP1, while STRING database and CytoHubba were used to construct protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) networks, respectively. An overall survival (OS) prognostic model was constructed to test the predictive efficacy of TAP1, and its effect on the in vitro proliferation activity and metastatic potential of UVM cell line C918 cells was verified by RNA interference.ResultsThere was a clear association between TAP1 expression and UVM patient prognosis. Upregulated TAP1 was strongly associated with a shorter survival time, higher likelihood of metastasis, and higher mortality outcomes. According to GSEA analysis, various immunity-related signaling pathways such as primary immunodeficiency were enriched in the presence of elevated TAP1 expression. A PPI network and a ceRNA network were constructed to show the interactions among mRNAs, miRNAs, and lncRNAs. Furthermore, TAP1 expression showed a significant positive correlation with immunoscore, stromal score, CD8+ T cells, and dendritic cells, whereas the correlation with B cells and neutrophils was negative. The Cox regression model and calibration plots confirmed a strong agreement between the estimated OS and actual observed patient values. In vitro silencing of TAP1 expression in C918 cells significantly inhibited cell proliferation and metastasis.ConclusionsThis study is the first to demonstrate that TAP1 expression is positively correlated with clinicopathological factors and poor prognosis in UVM. In vitro experiments also verified that TAP1 is associated with C918 cell proliferation, apoptosis, and metastasis. These results suggest that TAP1 may function as an oncogene, prognostic marker, and importantly, as a novel therapeutic target in patients with UVM.

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RRM2 is a potential prognostic biomarker with functional significance in glioma.

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RRM2 is a potential prognostic biomarker with functional significance in glioma.

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