Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1

摘要: The RNase III endonuclease Dicer plays a key role in generation of microRNAs (miRs). We hypothesized that regulates cancer cell susceptibility to immune surveillance through miR processing. Indeed, disruption up-regulated intercellular adhesion molecule (ICAM)-1 and enhanced the tumor cells antigen-specific lysis by cytotoxic T-lymphocytes (CTLs), while expression other immunoregulatory proteins examined was not affected. Blockade ICAM-1 inhibited specific CTLs against Dicer-disrupted cells, indicating pivotal interaction between CTL. Both miR-222 -339 are down-regulated directly interacted with 3′ untranslated region (UTR) mRNA. Modulation or these miRs inversely correlated protein U87 glioma CTL-mediated cytolysis mRNA levels remained stable. Immunohistochemical situ hybridization analyses 30 primary glioblastoma tissues demonstrated Dicer, miR-222, miR-339 associated expression. Taken together, is responsible for mature -339, which suppress on thereby down-regulating cytolysis. This study suggests development novel miR-targeted therapy promote cells.