MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma
Metrics: PDF 2710 views | HTML 3651 views | ?
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
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.