title: Restoration of miR17/20a in solid tumor cells enhances the natural killer cell antitumor activity by targeting Mekk2.
abstract: Aberrant microRNA (miRNA) expression has been identified in various human solid cancers. However, whether the levels of miRNA expression in tumor cells have any effect on tumor progression has not been determined. In this proof-of-concept study, the restoration of high-level expression of the miR17-92 cluster of miRNAs reveals its function as a tumor suppressor in murine solid cancer cells. Specifically, genetically engineered expression of higher levels of miR17/20a in the miR17-92 cluster in both murine breast cancer and colon cancer cells triggered natural killer (NK)-cell recognition by inhibiting the expression of MHC class I (H-2D) through the Mekk2-Mek5-Erk5 pathway. Results from the mouse tumor studies were recapitulated using samples of human solid tumors. Together, these data indicate that miR17/20a miRNAs function as tumor suppressors by reprogramming tumor cells for NK cell-mediated cytotoxicity.
authors.affiliation: Louisville Veterans Administration Medical Center; James Graham Brown Cancer Center; H0Zhan17@louisville.edu hongjiang.res@gmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei; and.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Li
authors.affiliation: James Graham Brown Cancer Center;
authors.forename: Qilong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: James Graham Brown Cancer Center;
authors.forename: Zhong-Bin
authors.initials: ZB
authors.lastname: Deng
authors.affiliation: James Graham Brown Cancer Center;
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: James Graham Brown Cancer Center;
authors.forename: Jingyao
authors.initials: J
authors.lastname: Mu
authors.affiliation: James Graham Brown Cancer Center;
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: James Graham Brown Cancer Center;
authors.forename: Baomei
authors.initials: B
authors.lastname: Wang
authors.affiliation: James Graham Brown Cancer Center;
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: James Graham Brown Cancer Center;
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.affiliation: Louisville Veterans Administration Medical Center; James Graham Brown Cancer Center; Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky; H0Zhan17@louisville.edu hongjiang.res@gmail.com.
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D048730:MAP Kinase Kinase Kinase 2 / Q000276:immunology; D020930:MAP Kinase Kinase Kinases / Q000276:immunology*; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000276:immunology*; D048054:Mitogen-Activated Protein Kinase 7 / Q000276:immunology; D047368:Tumor Burden
chemical_list: C524941:MIRN17 microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; C532375:Mirn20 microRNA, mouse; D048054:Mitogen-Activated Protein Kinase 7; D048730:MAP Kinase Kinase Kinase 2; D020930:MAP Kinase Kinase Kinases; C482618:MAP3K2 protein, human; C482619:Map3k2 protein, mouse