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Lan F.,Tianjin Hospital | Yu H.,Peking University | Hu M.,Shandong Academy of Sciences | Xia T.,PLA Airforce General Hospital | Yue X.,Tianjin Huanhu Hospital
Journal of Neurochemistry | Year: 2015

The study aimed to explore the specific function and mechanism of miR-144-3p in glioblastoma (GBM) cells with different phosphatase and tensin homolog (PTEN) phenotypes. We demonstrated that the miR-144-3p level was significantly down-regulated in glioma compared with the non-neoplastic brain tissues, and decreased with ascending grades. The loss of miR-144-3p effectively predicted the decreased overall survival in glioma patients. Interestingly, the expression of MET was up-regulated and inversely associated with miR-144-3p level in glioma tissues. Next, we certified that miR-144-3p specifically bound to MET 3′-untranslated region (3′ UTR) and inhibited its expression. miR-144-3p potently repressed GBM cell proliferation and invasion via suppressing MET in vitro and in vivo. In addition, our results showed no difference in malignancy inhibition induced by miR-144-3p in GBM cells with different PTEN phenotypes. miR-144-3p inhibited several survival signaling pathways by targeting MET independent of PTEN status in GBM cells. Over-expression of miR-144-3p inhibited survival capability and increased apoptosis, resulting in enhancement of radiation and temozolomide sensitivity. Our data provide new insights into the potential application of miR-144-3p in GBM therapy by targeting MET and then inhibiting the downstream signaling. © 2015 International Society for Neurochemistry. Source

Lan F.,PLA Airforce General Hospital | Yue X.,Tianjin Neurosurgery Institute | Ren G.,PLA Airforce General Hospital | Wang Y.,PLA Airforce General Hospital | Xia T.,PLA Airforce General Hospital
International Journal of Clinical and Experimental Pathology | Year: 2014

Objective: Toll-like receptors (TLRs) are highly or lowly expressed in a wide variety of tumors and exhibit either pro-tumor or anti-tumor activities. In the present study, we investigate whether there are relationships between the expressions of TLRs and the occurrence of radiation pneumonia in advanced NSCLC patients treated with radiotherapy. Materials and methods: 76 patients diagnosed with NSCLC and 50 healthy controls were recruited from Oct 2012 to Jan 2014. The expressions of serum TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR9 were detected by ELISA techniques. Fisher exact test, x2 test, ROC working curve and Cox regression model were applied to analyze all data. Results: serum TLR1, TLR2, TLR4, and TLR9 exhibited a relative high expression level in NSCLC patients compared with healthy controls. Importantly, pre-neutrophil granulocyte ratio was associated with the expression of TLR1, TLR2, and TLR4. Moreover, the patients with high ratio of neutrophil granulocyte significantly increased the occurrence of fever in comparison to normal neutrophil ratio in NSCLC patients during the course of radiotherapy. We further evaluated the containing of TLRs when patients had temperatures and found serum TLR1, TLR2 and TLR4 were over-expressed. Finally, 26 of 76 patients were diagnosed with different stages of radiation induced pneumonia; as a result, the contents of TLR1 and TLR4 before radiotherapy were identified as independent significances with pneumonia occurrence. Conclusions: The pretreatment levels of TLR1 and TLR4 have the predictive value to be clinically potential biomarkers of pneumonia risk in locally advanced NSCLC. Source

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