MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: Potential implications for immune based therapy of human solid tumors Journal Article

   

Authors:	Xu, H.; Cheung, I. Y.; Guo, H. F. ; Cheung, N. K. V.
Article Title:	MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: Potential implications for immune based therapy of human solid tumors
Abstract:	B7-H3, a surface immunomodulatory glycoprotein, inhibits natural killer cells and Tcells. The monoclonal antibody (mAb) 8H9 is specific for 4Ig-B7-H3, the long and principal form of B7-H3. Early results from radioimmunotherapy using 8H9 have shown promise in patients with metastatic solid tumors to the central nervous system. Whereas B7-H3 transcript was ubiquitously expressed in a wide spectrum of human solid tumors as well as human normal tissues, B7-H3 protein was preferentially expressed only in tumor tissues. By quantitative reverse transcription-PCR, all three isoforms of microRNA miR-29 (a, b, and c) were highly expressed in normal tissues. However, they were down-regulated in a broad spectrum of solid tumors, including neuroblastoma, sarcomas, brain tumors, and tumor cell lines. B7-H3 protein expression was inversely correlated with miR-29 levels in both cell lines and tumor tissues tested. Using luciferase reporter assay, miR-29a was shown to directly target B7-H3 3′ untranslated region, and knock-in and knockdown of miR-29a led to down-regulation and up-regulation, respectively, of B7-H3 protein expression. The ability of miR-29 to control B7-H3 protein expression has implications in immune escape by solid tumors. Differential modulation of this key immunoinhibitory molecule in tumor versus normal tissues may advance both cell-mediated immunotherapy and antibody-based targeted strategies using the B7-H3-specific mAb 8H9. ©2009 American Association for Cancer Research.
Keywords:	controlled study; human tissue; protein expression; unclassified drug; human cell; nonhuman; solid tumor; drug targeting; flow cytometry; protein function; protein localization; neoplasms; cancer immunotherapy; reverse transcription polymerase chain reaction; microrna; luciferase; immunoglobulin; cancer cell culture; immunofluorescence; cell line, tumor; hela cells; monoclonal antibody; antibodies, monoclonal; correlation analysis; transcription regulation; antigens, neoplasm; messenger rna; neuroblastoma cell; reverse transcriptase polymerase chain reaction; rna, messenger; quantitative analysis; membrane protein; western blotting; brain metastasis; cell fractionation; immunomodulating agent; antigens, cd; micrornas; glycoprotein; isoprotein; 3' untranslated regions; receptors, immunologic; b7 h3 protein; microrna 29; microrna 29 a; microrna 29 b; microrna 29 c; monoclonal antibody 8 h9; monoclonal antibody mab 1027; pronase; immunoaffinity chromatography
Journal Title:	Cancer Research
Volume:	69
Issue:	15
ISSN:	0008-5472
Publisher:	American Association for Cancer Research
Date Published:	2009-08-01
Start Page:	6275
End Page:	6281
Language:	English
DOI:	10.1158/0008-5472.can-08-4517
PUBMED:	19584290
PROVIDER:	scopus
PMCID:	PMC2719680
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-68049117231&partnerID=40&md5=68edbdd9093e018c6111dc1695fd983b
Notes:	--- - "Cited By (since 1996): 15" - "Export Date: 30 November 2010" - "CODEN: CNREA" - "Source: Scopus"

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