title: Ovarian tumor-associated microRNA-20a decreases natural killer cell cytotoxicity by downregulating MICA/B expression.
abstract: MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs, and changes in miRNAs are involved in tumor origin and progression. Studies have shown that miR-20a is overexpressed in human ovarian cancer tissues and that this miRNA enhances long-term cellular proliferation and invasion capabilities. In this study, a positive correlation between serum miR-20a expression and ovarian cancer stage was observed. We found that miR-20a binds directly to the 3'-untranslated region of MICA/B mRNA, resulting in its degradation and reducing its protein levels on the plasma membrane. Reduction of membrane-bound MICA/B proteins, which are ligands of the natural killer group 2 member D (NKG2D) receptor found on natural killer (NK) cells, γδ(+) T cells and CD8(+) T cells, allows tumor cells to evade immune-mediated killing. Notably, antagonizing miR-20a action enhanced the NKG2D-mediated killing of tumor cells in both in vitro and in vivo models of tumors. Taken together, our data indicate that increased levels of miR-20a in tumor cells may indirectly suppress NK cell cytotoxicity by downregulating MICA/B expression. These data provide a potential link between metastasis capability and immune escape of tumor cells from NK cells.
authors.affiliation: Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Xie
authors.affiliation: Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Mengna
authors.initials: M
authors.lastname: Liu
authors.affiliation: Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1] Immunology and Reproductive Biology Lab of Medical School, Nanjing University, Nanjing 210093 [2] Immunology and Reproductive Biology Lab of Medical School, Nanjing University, Nanjing 210093.
authors.forename: Yunzhong
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Qiongyu
authors.initials: Q
authors.lastname: Mi
authors.affiliation: 1] Nanjing First Hospital, Nanjing Medical University, Nanjing, China [2] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002277:Carcinoma / Q000175:diagnosis* / Q000276:immunology* / Q000401:mortality; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000276:immunology* / Q000401:mortality; D011379:Prognosis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016019:Survival Analysis; D019139:Tumor Escape / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; C098080:MICB antigen; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta