Quantitative Proteomics Reveals that miR-155 Regulates the PI3K-AKT Pathway in Diffuse Large B-Cell Lymphoma

• Published in: The American journal of pathology Vol. 181; no. 1; pp. 26 - 33
• Main Authors: Huang, Xin, Shen, Yulei, Liu, Miao, Bi, Chengfeng, Jiang, Chunsun, Iqbal, Javeed, McKeithan, Timothy W, Chan, Wing C, Ding, Shi-Jian, Fu, Kai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2012; American Society for Investigative Pathology
• Subjects: 3' Untranslated Regions - genetics; Cell Line, Tumor; Gene Knockdown Techniques; Humans; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - physiology; Pathology; Phosphatidylinositol 3-Kinase - genetics; Phosphatidylinositol 3-Kinase - metabolism; Proteomics - methods; Proto-Oncogene Proteins c-akt - metabolism; RNA, Neoplasm - genetics; Short Communication; Signal Transduction - genetics; Transcription, Genetic
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2012.03.013

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 (p85α), 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 p85α 3′-untranslated region, and overexpression of miR-155 down-regulated both the transcription and translation of p85α. 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 AKT 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.