Authors

Lin Wang, State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China
Zhu-Mei Shi, State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Cheng-Fei Jiang, State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, ChinaFollow
Xue Liu, State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, ChinaFollow
Qiu-Dan Chen, State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, ChinaFollow
Xu Qian, State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China
Dong-Mei Li, State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, ChinaFollow
Xin Ge, State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, ChinaFollow
Xie-Feng Wang, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Ling-Zhi Liu, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaFollow
Yong-Ping You, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Ning Liu, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaFollow
Bing-Hua Jiang, State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United StatesFollow

Document Type

Article

Publication Date

7-30-2014

Comments

This article has been peer reviewed. It was published in: Oncotarget.

Volume 5, Issue 14, 2014, Pages 5416-5427.

Copyright © The Authors

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.

PubMed ID

24980823

Included in

Pathology Commons

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