title: Dynamically expressed microRNA-15b modulates the activities of CD8+ T lymphocytes in mice with Lewis lung carcinoma.
abstract: BACKGROUND
  CD8+ T cells are key members of adaptive immunity against tumorigenesis. As subset of CD8+ T cells, effector T cells (Te) and memory T cells (Tm) have different biological activities. The former can kill tumor cells but come into apoptosis in a certain period and the latter is static with the ability of self-renewal. Previous studies showed that microRNAs (miRNA) played critical roles in regulating adaptive immunity. This study aimed to identify the different expression of miRNAs between Te and Tm cells in tumor-bearing mice and to sort out the target miRNAs which can be regulated to improve anti-tumor activities of CD8+ T cells.
  
  
  METHODS
  miRNA expression profiling was performed on CD8+ Te and Tm cells from mice with Lewis lung carcinoma. Differentially expressed miRNA (miRNA-15b) was chosen and analyzed by qRT-PCR. Then, flow cytometry, ELISA, and CFSE kit were used to evaluate the biological effects of miRNA-15b on apoptosis, cytokine secretion, phenotype, and proliferation of CD8+ T cell. The possible downstream target genes of this miRNA were also analyzed.
  
  
  RESULTS
  Analysis of miRNA microarray and qRT-PCR showed that the level of miRNA-15b was higher in CD8+ Tm cells than in Te cells. Higher expression of miRNA-15b was observed in CD8+ T cells from tumor-bearing mice than those from healthy ones. Transfection of CD8+ T cells with miRNA-15b mimics could prevent T cells from apoptosis by inhibiting the translation of DEDD (Death Effector Domain-containing DNA binding protein). Moreover, ectopic miRNA-15b could inhibit the activation of CD8+ T cells (via repressing the production of IL-2 and IFN-γ and expression of CD69) and promote expression of CD44 through unknown pathways.
  
  
  CONCLUSIONS
  Up-regulation of miRNA-15b in tumor environment might negatively regulate anti-tumor immunity through inhibiting function of CD8+ T cells. miRNA-15b might be a potential therapeutic target for immunotherapy.
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Guocheng
authors.initials: G
authors.lastname: Zhong
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Cheng
authors.forename: Haixia
authors.initials: H
authors.lastname: Long
authors.forename: Luhang
authors.initials: L
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Qi
authors.forename: Tong
authors.initials: T
authors.lastname: Xiang
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D008175:Lung Neoplasms / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D035683:MicroRNAs; C570833:Mirn15 microRNA, mouse