miR-423-5p contributes to a malignant phenotype and temozolomide chemoresistance in glioblastomas.

作者: Shouwei Li , Ailiang Zeng , Qi Hu , Wei Yan , Yanwei Liu

DOI: 10.1093/NEUONC/NOW129

关键词:

摘要: Background Gliomas are based on a genetic abnormality and present with dismal prognosis. MicroRNAs (miRNAs) considered to be important mediators of gene expression in glioma tissues. Methods Real-time PCR was used analyze the microRNA-423-5p (miR-423-5p) human samples normal brain tissue. Apoptosis, cell cycle, proliferation, immunostaining, transwell, vitro 2D 3D migration, chemosensitivity assays were performed assess phenotypic changes cells overexpressing miRNA-423-5p. Western blotting determine inhibitor growth 4 (ING-4)in tissues, luciferase reporter assay conducted confirm whether ING-4 is direct target miR-423-5p. identify potential signaling pathways that affected by Xenograft tumors examined vivo for carcinogenic effects miR-423-5p Results We first reported increased gliomas tumor promoter via targeting ING-4. The overexpression resulted upregulation molecules such as p-AKT p-ERK1/2. In clinical samples, dysregulated, corresponding alteration observed (P = .0207). Furthermore, strengthened angiogenesis, invasion. Finally, also GBM neurosphere formation rendered resistant temozolomide (TMZ). Conclusion This study establishes functions an oncogene tissues suppressing suggests it has therapeutic glioma.

参考文章(30)
Ettore Appella, Mariko Kitahama-Shiseki, Remy M. Pedeux, Masayuki Shiseki, Curtis C. Harris, Makoto Nagashima, Jun Yokota, Koh Miura, Yuichiro Higashimoto, Hitoshi Onogi, Shu Okamura, p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer Research. ,vol. 63, pp. 2373- 2378 ,(2003)
Wei Yan, Yanwei Liu, Pei Yang, Zheng Wang, Yongping You, Tao Jiang, MicroRNA profiling of Chinese primary glioblastoma reveals a temozolomide-chemoresistant subtype Oncotarget. ,vol. 6, pp. 11676- 11682 ,(2015) , 10.18632/ONCOTARGET.3258
Dongfeng Han, Wenjin Wei, Xincheng Chen, Yaxuan Zhang, Yingyi Wang, Junxia Zhang, Xiefeng Wang, Tianfu Yu, Qi Hu, Ning Liu, Yongping You, NF-κB/RelA-PKM2 mediates inhibition of glycolysis by fenofibrate in glioblastoma cells Oncotarget. ,vol. 6, pp. 26119- 26128 ,(2015) , 10.18632/ONCOTARGET.4444
Justin D. Lathia, John M. Heddleston, Monica Venere, Jeremy N. Rich, Deadly Teamwork: Neural Cancer Stem Cells and the Tumor Microenvironment Cell Stem Cell. ,vol. 8, pp. 482- 485 ,(2011) , 10.1016/J.STEM.2011.04.013
Chang-Zheng Chen, MicroRNAs as Oncogenes and Tumor Suppressors The New England Journal of Medicine. ,vol. 353, pp. 1768- 1771 ,(2005) , 10.1056/NEJMP058190
Karl H. Plate, Alexander Scholz, Daniel J. Dumont, Tumor angiogenesis and anti-angiogenic therapy in malignant gliomas revisited Acta Neuropathologica. ,vol. 124, pp. 763- 775 ,(2012) , 10.1007/S00401-012-1066-5
Xu Qian, Jing Yu, Yu Yin, Jun He, Ling Wang, Qi Li, Lou-Qian Zhang, Chong-Yong Li, Zhu-Mei Shi, Qing Xu, Wei Li, Li-Hui Lai, Ling-Zhi Liu, Bing-Hua Jiang, MicroRNA-143 inhibits tumor growth and angiogenesis and sensitizes chemosensitivity to oxaliplatin in colorectal cancers. Cell Cycle. ,vol. 12, pp. 1385- 1394 ,(2013) , 10.4161/CC.24477
XiaoMei Li, LiMin Cai, Hui Chen, QingYuan Zhang, ShuJun Zhang, YanHua Wang, YanYan Dong, Hui Cheng, JiPing Qi, Inhibitor of Growth 4 Induces Growth Suppression and Apoptosis in Glioma U87MG Pathobiology. ,vol. 76, pp. 181- 192 ,(2009) , 10.1159/000218334
Andrew H. Coles, Stephen N. Jones, The ING gene family in the regulation of cell growth and tumorigenesis. Journal of Cellular Physiology. ,vol. 218, pp. 45- 57 ,(2009) , 10.1002/JCP.21583