title: Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma.
abstract: 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.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Yulei
authors.initials: Y
authors.lastname: Shen
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Bi
authors.forename: Chunsun
authors.initials: C
authors.lastname: Jiang
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Timothy W
authors.initials: TW
authors.lastname: McKeithan
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Shi-Jian
authors.initials: SJ
authors.lastname: Ding
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt