RAB38 confers a poor prognosis, associated with malignant progression and subtype preference in glioma
ABSTRACT RAB38 is a new member of the RAB small G protein family that regulates intracellular vesicle trafficking. RAB38 is expressed in melanocytes and it has been shown that a point mutation in the postulated GTP-binding domain of RAB38 is the gene responsible for human Hermansky-Pudlak syndrome. However, the prognostic and molecular features of tumors with RAB38 expression is still unclear, as well as glioma. Whole genome mRNA expression microarray data on 220 glioma samples from the Chinese glioma genome atlas (CGGA) database (http://www.cgga.org.cn) was applied as discovery set. Each grade of glioma patients was analyzed by the Kaplan-Meier method. To determine the protein expression levels of RAB38, further 82 glioma tissues were stained by immunohistochemistry. Three additional datasets (TCGA, GSE16011 and Rembrandt) were obtained as validation sets. The functional annotation of RAB38 was analyzed by Gene ontology (GO) analysis and Gene set variation analysis (GSVA) in 89 glioblastomas (GBMs). High RAB38 expression was mainly increased in high-grade gliomas, and high RAB38 expression also conferred high mortality of glioma in the CGGA cohort. RAB38 showed a mesenchymal subtype, G3 subtype and isocitrate dehydrogenase 1 (IDH1) wild-type preference. GO and GSVA analysis showed that RAB38 was significantly correlated with migration. These results were validated in other 3 datasets. The expression levels of RAB38 were significantly associated with grade progression as well as prognosis in gliomas. RAB38 is an important prognostic biomarker and potential therapeutic target in gliomas.
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ABSTRACT: Glioblastoma are highly aggressive brain tumors with poor prognosis. While various dysregulation of signaling pathways in gliomas have been described, the identification of biomarkers and therapy targets remains an important task for novel diagnostic and therapeutic approaches. Here we described that the Suppressor of fused (also known as Sufu) is significantly down-regulated in high-grade gliomas, correlating with a poor prognosis. We demonstrated that ectopic expression of Sufu inhibited cell proliferation, invasion and vasculogenic mimicry. In addition, overexpression of Sufu reduced Gli reporter gene transcription activity and prevented Gli1 nuclear accumulation, whereas knockdown of Sufu reversed these effects. Furthermore, overexpressed Sufu sensitized glioblastoma to Temozolomide and Cyclopamine. Thus, Sufu is potential tumor suppressor and therapeutic target in glioblastoma.Oncotarget 10/2014; 5(22). · 6.63 Impact Factor
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ABSTRACT: miR-200b is a tumor suppressor in multiple tumors including gastric cancer, breast cancer, ovarian cancer and glioma. In this study, we detected the expression of miR-200b and analyzed its correlation with clinicopathological parameters in glioma tissues. miR-200b was downregulated in glioma tissues. And its downexpression was correlated with poor prognosis in gliomas. Members of RAB family, RAB21, RAB23, RAB18 and RAB3B were predicted to be novel targets of miR-200b. The direct suppression of RAB21, RAB23, RAB18 and RAB3B expressions by miR-200b was revealed by luciferase reporter assay, quantitative RT-PCR analysis and Western blot. Furthermore, the overall survival of patients with different expression of RABs was analyzed. The expression of RAB21, RAB23, RAB18 and RAB3B was related to the prognosis and histopathology of glioma. The patients who had the upregulation of all the four RABs had the worst outcome; those who had the downregulation of all RABs had the best outcome (p < 0.001). miR-200b was a potential biomarker for glioma prognosis.Medical Oncology 03/2014; 31(3):859. DOI:10.1007/s12032-014-0859-x · 2.06 Impact Factor