1. MiR-203 downregulation is responsible for chemoresistance in human glioblastoma by promoting epithelial-mesenchymal transition via SNAI2
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Tianzhu Liu, Xin Wang, Xiaohui Yan, Lei Zheng, Shengcong Qiu, Lianyan Huang, Hongbo Guo, Ningbo Xu, Yifeng Bai, Yanting Liu, and Hongzhan Liao
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Adult ,Male ,chemotherapy resistance ,Pathology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,SNAI2 ,Down-Regulation ,Antineoplastic Agents ,Drug resistance ,Biology ,Transfection ,Small hairpin RNA ,Cell Movement ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Neoplasm Invasiveness ,RNA, Neoplasm ,Epithelial–mesenchymal transition ,RNA, Small Interfering ,U87 ,3' Untranslated Regions ,Cell Shape ,Protein Kinase Inhibitors ,Aged ,Brain Neoplasms ,Gene Expression Profiling ,glioblastoma ,Cancer ,Middle Aged ,medicine.disease ,Drug Resistance, Multiple ,Neoplasm Proteins ,microRNAs ,Gene Expression Regulation, Neoplastic ,Imatinib mesylate ,Oncology ,Drug Resistance, Neoplasm ,Imatinib Mesylate ,Cancer research ,Female ,RNA Interference ,Snail Family Transcription Factors ,miR-203 ,Transcription Factors ,Research Paper - Abstract
// Hongzhan Liao 1,* , Yifeng Bai 2,* , Shengcong Qiu 1 , Lei Zheng 3 , Lianyan Huang 4 , Tianzhu Liu 1 , Xin Wang 1 , Yanting Liu 1 , Ningbo Xu 1 , Xiaohui Yan 5 and Hongbo Guo 1 1 Department of Neurosurgery, Neurosurgery Institute of Guangdong, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital, Southern Medical University, Guangzhou, China 2 Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, China 3 Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China 4 School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China 5 Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China * These authors contributed equally to this work Correspondence to: Hongbo Guo, email: // Keywords : chemotherapy resistance, epithelial-mesenchymal transition, microRNAs, glioblastoma, SNAI2 Received : January 16, 2015 Accepted : February 10, 2015 Published : March 12, 2015 Abstract Epithelial-mesenchymal transition (EMT) has been recognized as a key element of cell migration, invasion, and drug resistance in several types of cancer. In this study, our aim was to clarify microRNAs (miRNAs)-related mechanisms underlying EMT followed by acquired resistance to chemotherapy in glioblastoma (GBM). We used multiple methods to achieve our goal including microarray analysis, qRT-PCR, western blotting analysis, loss/gain-of-function analysis, luciferase assays, drug sensitivity assays, wound-healing assay and invasion assay. We found that miR-203 expression was significantly lower in imatinib-resistant GBM cells (U251AR, U87AR) that underwent EMT than in their parental cells (U251, U87). Ectopic expression of miR-203 with miRNA mimics effectively reversed EMT in U251AR and U87AR cells, and sensitized them to chemotherapy, whereas inhibition of miR-203 in the sensitive lines with antisense oligonucleotides induced EMT and conferred chemoresistance. SNAI2 was identified as a direct target gene of miR-203. The knockdown of SNAI2 by short hairpin RNA (shRNA) inhibited EMT and drug resistance. In GBM patients, miR-203 expression was inversely related to SNAI2 expression, and those tumors with low expression of miR-203 experienced poorer clinical outcomes. Our findings indicate that re-expression of miR-203 or targeting SNAI2 might serve as potential therapeutic approaches to overcome chemotherapy resistance in GBM. more...
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- 2015
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