Hepatosellüler karsinoma mikrodizin ekspresyon verilerinin in silico modellenmesi

Abstract

Bu çalışmada, HCC hücrelerinde Lityum etkisi ile meydana gelen proliferasyon inhibisyonunda, ekspresyonu transkript düzeyinde değişen genler ve bu genlerin yer aldığı sinyal yolaklarının tanımlanması için, Huh7 hücre hattı kullanılarak elde edilen ekspresyon mikrodizini veri setleri çözümlendi. İlk olarak, 48 saat, 20 mM LiCl uygulanmış ve uygulanmamış Huh7 hücrelerinden elde edilen, genom düzeyinde ekspresyon profilleri, Mikrodizin Anlamlılık Analizi yöntemi kullanılarak analiz edildi. İstatistiksel anlamlılık testi sonrası, Huh7 hücre hattında kontrole kıyasla anlamlı olarak artma ve azalma gösteren 1807 genin var olduğunu tespit edildi. (FDR In this study, the expression microarray data sets were obtained by using Huh7 cell line were analyzed to identify the genes, expressions of those changed at transcript-level during proliferation inhibition by the action of Lithium in HCC cells, and the pathways involving those genes. Firstly, the genome-wide expression profiles obtained from Huh7 cells treated with 20 mM LiCl for 48 hours and untreated, were analyzed using Significance Analysis of Microarray method. After statistical significance testing, it was determined that there were significantly up and down regulated 1807 genes in Huh7 cell line in comparison to control condition (FDR<0.01). After annotation analysis of significantly affected genes, 142 different pathways related to significant genes in Huh7 cell line were found and 18 out of these pathways were determined as statistically significant (p<0.01). Also, Gene Ontology term analysis showed that significantly up and down regulated genes were involved in diverse biological processes and molecular functions. Through the promoter analysis of two different gene clusters bearing up and down regulated genes with 4 or greater than 4 fold change, the possible common nucleotide motifs located the promoter regions of the genes in each gene cluster was determined. In conclusion, we believe that further analysis of the significant genes obtained from the data sets with additional molecular biological methods will help to understand the underlying molecular mechanism of Lithium effects on proliferation inhibition in Huh7 cells.