Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 181, Issue 1, Pages 26-33Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2012.03.013
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Funding
- China Scholarship Council
- NIH [U01 CA114778-03]
- Nebraska Department of Health and Human Services [LB606]
- Lymphoma Research Foundation/Millennium Inc.
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The aberrant expression of microRNA-155 (miR-155), which has emerged as having a significant impact on the biological characteristics of lymphocytes, plays important roles in B-cell malignancies, such as diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common non-Hodgkin's lymphoma in the adult population, accounting for approximately 40% of newly diagnosed non-Hodgkin's lymphoma cases globally. To determine the specific function of miR-155, a quantitative proteomics approach was applied to examine the inhibitory effects of miR-155 on protein synthesis in DLBCL cells. PIK3R1 (p85 alpha), a negative regulator of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, was identified as a direct target of miR-155. A luciferase reporter was repressed through the direct interaction of miR-155 and the p85 alpha 3'-untranslated region, and overexpression of miR-155 down-regulated both the transcription and translation of p85 alpha. The PI3K-AKT signaling pathway was highly activated by the sustained overexpression of miR-155 in DHL16 cells, whereas knockdown of miR-155 in OCI-Ly3 cells diminished AICT activity. Taken together, our results reveal a novel target involved in miR-155 biological characteristics and provide a molecular link between the overexpression of miR-155 and the activation of PI3K-AKT in DLBCL (Am J Pathol 2012, 181:26-33; http://dx.doi.org/10.1016/j.ajpath.2012.03.013)
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