Abstract 2027: Proteomic analysis identifies pathways regulated by miR-34a

Abstract MicroRNA 34a (miR-34a) is an important tumor suppressor gene and has been identified as a miRNA component of the p53 network. To better understand the biological pathways involved in miR-34a action, we performed parallel global protein and mRNA expression profiling on miR-34a treated neuroblastoma cells (IMR32 cells) using isotope-coded affinity tags (ICAT) and Affymetrix U133plus2 microarray respectively. Global profile suggests a mild overall mRNA expression changes in miR-34a treated cells, but systematic protein level changes have been detected. A total of 1495 proteins represented by 2 or more peptides were identified from the quantitative ICAT analysis, of which 143 and 192 proteins are significantly up- or down-regulated in miR-34a treated cells. Several of these down-regulated proteins contain seed sequences for miR-34a. Pathway analysis of the differentially expressed proteins shows the enrichment of apoptosis and cell death in up-regulated proteins, and DNA replication and cell cycle processes in the down-regulated proteins in miR-34a treated cells. Biological network analysis of direct interaction between differentially expressed proteins suggests that YY1 as well as its downstream proteins are significantly inhibited by miR-34a. Western blotting confirmed the suppression of YY1 protein expression by miR-34a. MiR-34a might target YY1 through miR-34a-binding site in the 3’ UTR of YY1. YY1 is a ubiquitous transcription factor and it is a negative regulator of p53. YY1 has been associated with cell proliferation, anti-apoptosis, tumorigenesis and metastatic potential. Therefore the elucidation of the role of YY1 may shed important light on tumor suppressive function of miRNA-34a. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2027.