Dataset Information

MiR-203 downregulation is responsible for chemoresistance in human glioblastoma by promoting epithelial-mesenchymal transition via SNAI2.

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.

SUBMITTER: Liao H

PROVIDER: S-EPMC4496192 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MiR-203 downregulation is responsible for chemoresistance in human glioblastoma by promoting epithelial-mesenchymal transition via SNAI2.

Liao Hongzhan H Bai Yifeng Y Qiu Shengcong S Zheng Lei L Huang Lianyan L Liu Tianzhu T Wang Xin X Liu Yanting Y Xu Ningbo N Yan Xiaohui X Guo Hongbo H

Oncotarget 20150401 11

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 assa ...[more]

PMID: 25871397

Similar Datasets

Project description:The aim of the present study was to investigate whether miR?203 can inhibit transforming growth factor?? (TGF??)?induced epithelial?mesenchymal transition (EMT), and the migration and invasion ability of non?small cell lung cancer (NSCLC) cells by targeting SMAD3. In the present study, the expression levels of miR?203, SMAD3 mRNA and protein in NSCLC tissues were examined, as well as their corresponding paracancerous samples. The miR?203 mimics and miR?203 inhibitor were transfected into the H226 cell line. RT?qPCR was used to assess the expression levels of E?cadherin, Snail, N?cadherin and vimentin mRNA, and western blotting was performed to detect the expression levels of p?SMAD2, SMAD2, p?SMAD3, SMAD3 and SMAD4. The cell migration and invasion abilities were detected by Transwell assays. The target site of SMAD3 was predicted by the combined action between miR?203 and dual luciferase. The results revealed that the RNA levels of miR?203, compared with paracancerous tissues, were decreased in NSCLC tissues, while SMAD3 mRNA and protein levels were upregulated, and miR?203 inhibited SMAD3 expression. Induction of TGF?? led to decreased E?cadherin mRNA levels, upregulation of Snail, N?cadherin and vimentin mRNA levels (P<0.05), and significant increase in cell migration and invasion, whereas transfection of miR?203 mimics reversed the aforementioned results (P<0.05). Conversely, miR?203 inhibitor could further aggravate the aforementioned results (P<0.05). Western blot results revealed that transfection of miR?203 mimics significantly reduced the protein expression of SMAD3 and p?SMAD3 (P<0.05). Furthermore, the results of the Dual?Luciferase assay revealed that miR?203 inhibited SMAD3 expression by interacting with specific regions of its 3'?UTR. Overall, a novel mechanism is revealed, in which, miR?203 can inhibit SMAD3 by interacting with specific regions of the 3'?UTR of SMAD3, thereby restraining TGF???induced EMT progression and migration and invasion of NSCLC cells.

Dataset Information

MiR-203 downregulation is responsible for chemoresistance in human glioblastoma by promoting epithelial-mesenchymal transition via SNAI2.

Publications

MiR-203 downregulation is responsible for chemoresistance in human glioblastoma by promoting epithelial-mesenchymal transition via SNAI2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure