miR-107 regulates tumor progression by targeting NF1 in gastric cancer.
Our previous genome-wide miRNA microarray study revealed that miR-107 was upregulated in gastric cancer (GC). In this study we aimed to explore its biological role in the pathogenesis of GC. Integrating in silico prediction algorithms with western blotting assays revealed that miR-107 inhibition enhanced NF1 (neurofibromin 1) mRNA and protein levels, suggesting that NF1 is one of miR-107 targets in GC. Luciferase reporter assay revealed that miR-107 suppressed NF1 expression by binding to the first potential binding site within the 3'-UTR of NF1 mRNA. mRNA stable assay indicated this binding could result in NF1 mRNA instability, which might contribute to its abnormal protein expression. Functional analyses such as cell growth, transwell migration and invasion assays were used to investigate the role of interaction between miR-107 and its target on GC development and progression. Moreover, We investigated the association between the clinical phenotype and the status of miR-107 expression in 55 GC tissues, and found the high expression contributed to the tumor size and depth of invasion. The results exhibited that down regulation of miR-107 opposed cell growth, migration, and invasion, whereas NF1 repression promoted these phenotypes. Our findings provide a mechanism by which miR-107 regulates NF1 in GC, as well as highlight the importance of interaction between miR-107 and NF1 in GC development and progression.
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.|Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.|Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
Shizhi
S
Wang
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.|Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Gaoxiang
G
Ma
Core Laboratory, Nantong Tumor Hospital, Nantong, China.
Haixia
H
Zhu
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.|Department of General Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.
Chunye
C
Lv
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.|Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Haiyan
H
Chu
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.|Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Na
N
Tong
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.|Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Dongmei
D
Wu
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.|Core Laboratory, Nantong Tumor Hospital, Nantong, China.
Fulin
F
Qiang
Department of General Surgery, Yixing Cancer Hospital, Yixing, China.
Weida
W
Gong
Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Qinghong
Q
Zhao
Department of General Surgery, Huai-An First People's Hospital Affiliated to Nanjing Medical University, Huai-An, China.
Guoquan
G
Tao
Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.
Jianwei
J
Zhou
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.|Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Zhengdong
Z
Zhang
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.|Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Meilin
M
Wang
D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
D020413:3' Untranslated Regions; C549045:MIRN107 microRNA, human; D035683:MicroRNAs; D025542:Neurofibromin 1