title: MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma.
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.
authors: State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China. These authors contributed equally to this work.
authors: Lin
authors: L
authors: Wang
authors: 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. These authors contributed equally to this work.
authors: Zhu-Mei
authors: ZM
authors: Shi
authors: State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China. These authors contributed equally to this work.
authors: Cheng-Fei
authors: CF
authors: Jiang
authors: State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors: Xue
authors: X
authors: Liu
authors: State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors: Qiu-Dan
authors: QD
authors: Chen
authors: State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors: Xu
authors: X
authors: Qian
authors: State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors: Dong-Mei
authors: DM
authors: Li
authors: State Key Lab of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors: Xin
authors: X
authors: Ge
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Xie-Feng
authors: XF
authors: Wang
authors: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, USA.
authors: Ling-Zhi
authors: LZ
authors: Liu
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Yong-Ping
authors: YP
authors: You
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Ning
authors: N
authors: Liu
authors: 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, USA.
authors: Bing-Hua
authors: BH
authors: Jiang
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D058990:Molecular Targeted Therapy; D015398:Signal Transduction; D000077204:Temozolomide; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D018906:Antineoplastic Agents, Alkylating; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D003606:Dacarbazine; D000077204:Temozolomide