Oncotarget

Research Papers:

MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma

Lin Wang, Zhu-mei Shi, Cheng-fei Jiang, Xue Liu, Qiu-dan Chen, Xu Qian, Dong-mei Li, Xin Ge, Xie-feng Wang, Ling-Zhi Liu, Yong-ping You, Ning Liu and Bing-Hua Jiang _

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Oncotarget. 2014; 5:5416-5427. https://doi.org/10.18632/oncotarget.2116

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Abstract

Lin Wang1,*, Zhu-mei Shi1,2,*, Cheng-fei Jiang1,*, Xue Liu1, Qiu-dan Chen1, Xu Qian1, Dong-mei Li1, Xin Ge1, Xie-feng Wang2, Ling-Zhi Liu3, Yong-ping You2, Ning Liu2 and Bing-Hua Jiang1,3

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.


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