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Objective:To explore the mechanism of miR-205-5p/E2F1 signal axis in regulating the glioma U251, U87 radiotherapy resistance.Methods:X-ray gradual ascending and intermittent induction method was used to irradiate the glioma U251 cells to establish U251/TR, U87/TR radiation-resistant cell lines. Then, the morphology, migration, invasion and proliferation abilities of cells (U251/TR, U87/TR radiation-resistant cells and U251, U87 radiation-sensitive cells) were analyzed. Luciferase gene detection system and point mutation technique were employed to analyze the mechanism of miR-205-5p and E2F1 gene activity on U251 and U87 radiation-resistant cell lines.Results:Compared with the radiation-sensitive U251 cells, the radiation-resistant cells U251/TR, U87/TR showed increased proliferation activity, enhanced migration and invasion abilities and decreased apoptosis under X-ray irradiation. miR-205-5p mimics transfection could down-regulate the expression of E2F1 factor in U251/TR cells, inhibit cell proliferation, invasion and migration and increase the radiosensitivity of U251/TR cells. miR-205-5p mimics transfection combined with with E2F1 down-regulation exerted anti-tumor effect and decreased cell tolerance by suppressing the Wnt/β-catenin signaling pathway activity.Conclusions:The glioma radiation-resistant cell line U251/TR, U87/TR can be established by X-ray gradual ascending and intermittent induction method. The miR-205-5p/E2F1 signal axis exerts tumor-suppressing effect through the classical Wnt/β-catenin signaling pathway, which can be used as an therapeutic target to increase the radiosensitivity of glioma.
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As an internal environment of tumor occurrence, tumor microenvironment is composed of a variety of cells and extracellular matrix, and plays a crucial role in tumor formation, transfer and resistance to drugs. The regulation of tumor microenvironment will be a potential target to control the cancer. MicroRNAs (miRNAs) are a kind of 21 to 25 nucleotides single-stranded RNA, and are mainly involved in regulating gene expression. Recently, with the suggestion of cellular auton-omous tumor inhibition mechanism, the regulation of tumor microenvironment by miRNAs has received great attention. This review summarizes recent findings on the non-cell-autonomous mechanisms of miRNAs-mediated regulation of tumor micro-environments, which provides foundations and perspective on the design of therapeutic interventions.
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Glioblastoma (GBM) is one of the WHO gradeⅣmalignancies, which is an acentral nervous system cancer with poor prognosis unless the lesion is in the brain stem. The incidence of GBM accounts for 80%of human primary malignant tumors in brain. Only 5%GBM can survive up to 5-years. Many researches showed that Sox2 is a pluripotent regulator, and muta?tion or abnormal function of Sox2 are closely related to the development of GBM. There are studies demonstrated the possibil?ity of using Sox2 gene as apotential target for GBM therapy. This paper reviewed recent progress in GBM.
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Objective To explore the role and expression of cell apoptosis regulatory genes in patients with temporal lobe epilepsy characterized by hippocampus sclerosis.Methods The experimental specimens were obtained from 15 patients with temporal lobe epilepsy (epilepsy group) and 6 control samples (control group) were obtained from temporal lobe excision of brain trauma decompression,investigated neuron apoptosis by HE stain,TdT-mediated dUTP-biotin nick end labeling (TUNEL) method,and determined the expression of bcl-2,bax and caspase-3 by immunohistochemistry.Results The evidence of neuron apoptosis was not found by HE stain in both control group and epilepsy group.Positive cells was not found in control group,but was obviously observed in epilepsy group by TUNEL staining [(4.39 ± 2.04) numbers/100].Unlike that in normal adult brain,bcl-2 immunoreactivity was obviously observed in some neurons in epilepsy group[(6.72 ± 3.36) numbers/100] (P ＜ 0.01).Compared with control group,bax protein in epilepsy group was mild expression (P ＞ 0.05).Two cases in control group were detected the expression of caspase-3 protein,and caspase-3 significantly increased in epilepsy group [(1.07 ± 0.43),(9.54 ± 3.68) numbers/100] (P ＜ 0.01).Conclusions Neuron apoptosis is an important cause of hippocampal sclerosis of human epilepsy.bcl-2 and caspase-3 may play an important role in this process.
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Aim To explore effects of TCS on the gene expression profiles of human cervical carcinoma HeLa cells with microarray technique and further investigate its molecular mechanism. Methods RNA from both control and treated HeLa cells were isolated and reversely transcribed to cDNA with the incorporation of cy3 and cy5-labeled dUTP, probes were hybridized with BiostarH-Ⅰ cDNA microarray, chips were scanned and then analyzed by GenePix Pro 3.0 software. Results 78 significantly differently expressed genes were screened out of which up-and down-regulated genes were 62 and 16 respectively. the up-regulated genes were closely related with apoptosis (such as NOP56、TNFSF10、CASP9、DFFB,etc) and the down-regulated genes were associated with the adhesion and interaction between cells (such as COL9A3、LGALS3BP、 MGST3,etc). Conclusion TCS could result in differential expression of multiple genes in HeLa cells, and DNA microarray technique can provide valuable insight into the molecular mechanism of TCS-induced apoptosis.