Shenzhen Key Laboratory of Neurosurgery
Shenzhen Key Laboratory of Neurosurgery
Ji T.,Anhui Medical University |
Zhang X.,Anhui Medical University |
Zhang X.,Shenzhen Key Laboratory of Neurosurgery |
Li W.,Anhui Medical University |
Li W.,Shenzhen Key Laboratory of Neurosurgery
Molecular Medicine Reports | Year: 2017
Glioma is the most common form of primary malignant tumor that occurs in the central nervous system. The underlying molecular mechanism of the carcinogenesis and progression of glioma remains to be elucidated. It is well-established that microRNAs (miRs) are associated with the regulation of glioma initiation and progression, and may represent a novel effective therapeutic strategy for the treatment of glioma. In the present study, the expression, roles and molecular mechanisms of miR-205 in glioma were investigated. The expression levels of miR-205 in glioma tissues, normal brain tissues, human glioma and normal HEB glial cell lines were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To explore the functional roles of miR-205 in glioma cells, a Cell Counting kit 8 assay, and Transwell migration and invasion assays were employed. The molecular mechanisms underlying the roles of miR-205 in glioma cells were investigated using bioinformatics analysis, a luciferase reporter assay, RT-qPCR and western blot analysis. The results of the present study demonstrated that miR-205 expression was markedly low in glioma tissues and cell lines compared with normal brain tissue and a glial cell line. Upregulation of miR-205 in vitro decreased cell viability, migration and invasion in glioma. Further investigation of the potential molecular mechanism demonstrated that the tumor suppressive functions of miR-205 in regulating the proliferation, migration and invasion of glioma cells were mediated by a direct target gene, yes associated protein 1 (YAP1). The results of the present study suggested that miR-205 inhibited glioma growth and metastasis by directly targeting YAP1, and that miR-205 should be investigated as a novel therapeutic target for anti-cancer treatment.
Li Z.-Y.,Shenzhen University |
Li Z.-Y.,Shenzhen Key Laboratory of Neurosurgery |
Zhang C.,Shenzhen University |
Zhang C.,Guangzhou University |
And 10 more authors.
Phytotherapy Research | Year: 2017
Glioblastoma multiforme (GBM) is the most frequent, lethal and aggressive tumour of the central nervous system (CNS) in adults. Multidrug resistance (MDR) results in undesirable prognosis during GBM chemotherapy. In this study, we determined that Radicol (RAD), a novel trinorguaiane-type sesquiterpene originally isolated from the root of Dictamnus radicis Cortex, exhibited potently cytotoxic effect on temozolomide (TMZ)-resistant GBM cell lines in a dose-dependent manner. Radicol-induced apoptosis was confirmed with Hoechst 33342/propidium iodide and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labelling (TUNEL) staining. Studies investigating the mechanism revealed that RAD triggered an attenuation of protein disulphide isomerase (PDI) and induced the unmitigated unfolded protein response (UPR) and lethal endoplasmic reticulum (ER) stress. Simultaneously, we further demonstrated that RAD suppressed the activation of Akt/mTOR/p70S6K phosphorylation by up-regulating the induction of glycogen synthase kinase-3β (GSK-3β). These results established a link between RAD-induced ER stress and inhibition of the Akt/mTOR/p70S6K pathway, and the attenuation of PDI and activation of GSK-3β might be the synergistic target of antineoplastic effects during RAD-induced apoptosis. These findings suggested that RAD, possessing multiple cytotoxicity targets, low molecular weight and high lipid solubility, could be a promising agent for the treatment of malignant gliomas. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.