MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma
| Autor: | Dong mei Li, Cheng fei Jiang, Lin Wang, Yong ping You, Zhu Mei Shi, Bing-Hua Jiang, Xue Liu, Xin Ge, Qiu Dan Chen, Xie feng Wang, Ling-Zhi Liu, Ning Liu, Xu Qian |
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| Rok vydání: | 2014 |
| Předmět: |
Male
MAPK/ERK pathway Angiogenesis Down-Regulation Mice Nude Apoptosis Biology Transfection Mice 03 medical and health sciences 0302 clinical medicine N-RAS Cell Line Tumor Glioma Neuroblastoma Temozolomide medicine Animals Humans Genes Tumor Suppressor Molecular Targeted Therapy Antineoplastic Agents Alkylating Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation 030304 developmental biology Tube formation Mice Inbred BALB C 0303 health sciences Brain Neoplasms medicine.disease Xenograft Model Antitumor Assays Molecular biology miR-143 3. Good health Dacarbazine MicroRNAs tumor growth Genes ras Oncology 030220 oncology & carcinogenesis Cancer research Research Paper Signal Transduction medicine.drug |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.2116 |
| Popis: | // Lin Wang 1,* , Zhu-mei Shi 1,2,* , Cheng-fei Jiang 1,* , Xue Liu 1 , Qiu-dan Chen 1 , Xu Qian 1 , Dong-mei Li 1 , Xin Ge 1 , Xie-feng Wang 2 , Ling-Zhi Liu 3 , Yong-ping You 2 , Ning Liu 2 and Bing-Hua Jiang 1,3 1 State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China 2 Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 3 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, USA * These authors contributed equally to this work Correspondence: Bing-Hua Jiang, email: // Ning Liu, email: // Keywords : miR-143, N-RAS, tumor growth, Glioma Received : April 18, 2014 Accepted : June 17, 2014 Published : June 18, 2014 Abstract Therapeutic applications of microRNAs (miRNAs) in RAS-driven glioma were valuable, but their specific roles and functions have yet to be fully elucidated. Here, we firstly report that miR-143 directly targets the neuroblastoma RAS viral oncogene homolog (N-RAS) and functions as a tumor-suppressor in glioma. Overexpression of miR-143 decreased the expression of N-RAS, inhibited PI3K/AKT, MAPK/ERK signaling, and attenuated the accumulation of p65 in nucleus of glioma cells. In human clinical specimens, miR-143 was downregulated where an adverse with N-RAS expression was observed. Furthermore, overexpression of miR-143 decreased glioma cell migration, invasion, tube formation and slowed tumor growth and angiogenesis in a manner associated with N-RAS downregulation in vitro and in vivo . Finally, miR-143 also sensitizes glioma cells to temozolomide (TMZ),the first-line drug for glioma treatment. Taken together, for the first time, our results demonstrate that miR-143 plays a significant role in inactivating the RAS signaling pathway through the inhibition of N-RAS, which may provide a novel therapeutic strategy for treatment of glioma and other RAS-driven cancers. |
| Databáze: | OpenAIRE |
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