Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MicroRNA profiling of human cholangiocytes in response to interferon-gamma

ABSTRACT: Cells of a human cholangiocyte cell line (H69) were exposed to 10 ng/ml of IFN-gamma for 8 h. Cells were collected and processed for miRNA array analysis carried out by EXIQON (Denmark).

ORGANISM(S): Homo sapiens

SUBMITTER: Xian-Ming Chen

PROVIDER: E-MEXP-1906 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes.

Gong Ai-Yu AY Zhou Rui R Hu Guoku G Li Xiaoqing X Splinter Patrick L PL O'Hara Steven P SP LaRusso Nicholas F NF Soukup Garrett A GA Dong Haidong H Chen Xian-Ming XM

Journal of immunology (Baltimore, Md. : 1950) 20090201 3

Biliary epithelial cells (cholangiocytes) respond to proinflammatory cytokines such as IFN-gamma and actively participate in the regulation of biliary inflammatory response in the liver. B7-H1 (also known as CD274 or PD-L1) is a member of the B7 costimulatory molecules and plays a critical immunoregulatory role in cell-mediated immune responses. In this study, we show that resting human cholangiocytes in culture express B7-H1 mRNA, but not B7-H1 protein. IFN-gamma induces B7-H1 protein expressio ...[more]

PMID: 19155478

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Project description: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. BALB/c mice (female, 6- to 8-wk-old) were injected subcutaneously in the mammary fat pad with 100,000 4T1 tumor cells. Three weeks later, tumor-bearing animals were used for the indicated studies. Gr-1+ CD11b+ cells were isolated by immunomagnetic selection from the bone marrow of 4T1 tumor-bearing mice (n=3) and tumor-free BALB/c mice (n=3), then the miRNA expression profile were analyzed using miRCURY LNAM-bM-^DM-" microRNA Arrays.

Dataset Information

MicroRNA profiling of human cholangiocytes in response to interferon-gamma

Publications

MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes.

Similar Datasets

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