title: Reduced miR-3127-5p expression promotes NSCLC proliferation/invasion and contributes to dasatinib sensitivity via the c-Abl/Ras/ERK pathway.
abstract: miR-3127-5p is a primate-specific miRNA which is down-regulated in recurrent NSCLC tissue vs. matched primary tumor tissue (N = 15) and in tumor tissue vs. normal lung tissue (N = 177). Reduced miR-3127-5p expression is associated with a higher Ki-67 proliferation index and unfavorable prognosis in NSCLC. Overexpression of miR-3127-5p significantly reduced NSCLC cells proliferation, migration, and motility in vitro and in vivo. The oncogene ABL1 was a direct miR-3127-5p target, and miR-3127-5p regulated the activation of the Abl/Ras/ERK pathway and transactivated downstream proliferation/metastasis-associated molecules. Overexpression of miR-3127-5p in A549 or H292 cells resulted in enhanced resistance to dasatinib, an Abl/src tyrosine kinase inhibitor. miR-3127-5p expression levels were correlated with dasatinib sensitivity in NSCLC cell lines without K-Ras G12 mutation. In conclusion, miR-3127-5p acts as a tumor suppressor gene and is a potential biomarker for dasatinib sensitivity in the non-mutated Ras subset of NSCLC.
authors.affiliation: 1] Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China [2] Department of Thoracic Surgery, Shanghai Chest Hospital Affiliated Shanghai Jiaotong University, No. 241, Huaihaixi Road, Shanghai, 200030, P.R. China [3].
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 1] Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China [2].
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.affiliation: 1] Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China [2].
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China.
authors.forename: Huikang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China.
authors.forename: Likun
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hui
authors.affiliation: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Departments of Gynaecology and Obstetrics, Shanghai First Maternity and Infant Health Hospital. Tongji University School of Medicine, No. 536, Changle Road, Shanghai, 200126, P.R. China.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital Affiliated Shanghai Jiaotong University, No. 241, Huaihaixi Road, Shanghai, 200030, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Gao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C000605234:MIRN3127 microRNA, human; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D013844:Thiazoles; D016315:Proto-Oncogene Proteins c-abl; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D018631:ras Proteins; D000069439:Dasatinib