In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 4087-4087
Abstract:
Ligands of the natural killer (NK) cells and CD8+ cytotoxic T lymphocyte (CTL) receptors, such as the inhibitory classical HLA-G antigen, are often deregulated upon viral infection and neoplastic transformation thereby allowing virus-infected or malignant-transformed cells to escape NK and T cell-mediated immune surveillance. The underlying molecular mechanisms controlling the aberrant HLA-G expression have been recently identified suggesting that cellular microRNAs (miRs) target the 3′UTR of HLA-G mRNA thereby shaping the anti-tumoral immune response. Functional analysis of these miRs demonstrated an inverse correlation of HLA-G and miR expression, which was directly associated with tumor grading, staging, disease progression and survival of renal cell carcinoma patients. Furthermore, these miRs enable tumors to evade NK and T cell cytotoxicity. Using 2DE-based proteome analysis in combination with MALDI-TOF mass spectrometry of HLA-G-specific miR transfectants and control cells lead to the identification of novel targets of these miRs including the 14-3-3-β protein (YWHAB). The miR-regulated YWHAB expression not only alters tumor cell proliferation, but also the sensitivity to apoptosis. Loss of HLA-G-specific miRs enhanced YWHAB expression, which is accompanied by an inhibition of pro-apoptotic gene expression leading to apoptosis resistance, enhanced proliferation, migration and tumor progression. Furthermore, YWHAB expression and lack of HLA-G-specific miR expression directly correlate with a worse clinical outcome of HLA-G+ tumors linking for the first time tumor immune escape mechanisms with the malignant phenotype. Thus, the HLA-G-regulating miRs not only affect immune surveillance, but also enhance tumorigenicity. Citation Format: Barbara Seliger, Simon Jasinski-Bergner, Juergen Bukur, Kristin Schulz, Franziska Stehle. Identification of microRNAs involved in shaping immune surveillance and growth properties of tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4087. doi:10.1158/1538-7445.AM2014-4087
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-4087
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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