Wqq_MDSC_miRNA Array
Ontology highlight
ABSTRACT: Myeloid-derived suppressor cells (MDSCs) potently suppress the anti-tumor immune responses and also orchestrate the tumor microenvironment that favors tumor angiogenesis and metastasis. The immunosuppressive activity of MDSCs has been extensively investigated, however the molecular networks regulating the non-immunological functions of tumor-expanded MDSCs, are largely unknown. In this study, we identified microRNA-494 (miR-494), whose expression was dramatically induced by tumor-derived factors (TDFs), as an essential player, in regulating the non-immunological activity of MDSCs by targeting PTEN and activating the Akt pathway. TGF-beta 1 was found to be a main tumor-derived factor responsible for the up-regulation of miR-494 in MDSCs. Expression of miR-494 not only enhanced CXCR4-mediated MDSC chemotaxis but also altered the intrinsic apoptotic/survival signal by targeting PTEN, thus contributing to the accumulation of MDSCs in tumor tissues. Consequently, down-regulation of PTEN resulted in increased activity of the Akt pathway and the subsequent up-regulation of matrix metalloproteinases (MMPs) for facilitating tumor cell invasion and metastasis. Knock down of miR-494 significantly reversed the activity of MDSCs and inhibited the tumor growth and metastasis of 4T1 murine breast cancer in vivo. Collectively, our findings reveal that TGF-beta 1-induced miR-494 expression in MDSCs plays a critical role in the molecular events governing the accumulation and non-immunological functions of tumor-expanded MDSCs, and might be identified as a potential target in cancer therapy.
ORGANISM(S): Rattus norvegicus Human gammaherpesvirus 8 Mus musculus Human alphaherpesvirus 1 JC polyomavirus Betapolyomavirus macacae Murid gammaherpesvirus 4 Homo sapiens Human immunodeficiency virus 1 Human betaherpesvirus 5 Betapolyomavirus hominis human gammaherpesvirus 4 Murid betaherpesvirus 1
PROVIDER: GSE36309 | GEO | 2012/03/20
SECONDARY ACCESSION(S): PRJNA153343
REPOSITORIES: GEO
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