Abstract 1519: Myb-regulated gene networks and signaling pathways in pancreatic cancer

Abstract

Abstract The MYB proto-oncogene (a cellular progenitor of v-Myb oncogene) encodes an oncogenic transcription factor that regulates the expression of a wide array of genes responsible for different cellular functions. We have recently identified MYB as a key driver of pancreatic cancer (PC) pathogenesis. Our findings demonstrated that MYB was overexpressed in majority of PC tissues and cell lines, while remained undetectable in normal pancreatic cells. In addition, MYB overexpression was shown to be associated with pancreatic tumor growth and metastasis. To gain further insight into the molecular mechanisms involved in MYB-potentiated effects in PC cells, we conducted Next-Generation Sequencing of transcriptome of control and MYB-silenced MiaPaCa cells on an Illumina HiSeq 2500 platform. By keeping a cut-off of fold change > 1.5 and p ≤ 0.05, we identified a total of 774 genes to be differentially expressed in MYB-altered MiaPaCa cells. Out of these, 485 genes were downregulated, while 289 genes exhibited upregulated expression. The differentially-regulated genes were subsequently analyzed for functions and cellular pathways alterations using Ingenuity Pathway Analysis (IPA) software. The top three networks to be affected in MYB knockdown PC cells included i) RNA post-transcriptional modifications, molecular transport, RNA trafficking, ii) cellular assembly and organization, cancer, and, iii) cell cycle, DNA replication, recombination and repair. These networks are centered on splicing factors, EGFR and NF-κB complex, respectively. IPA predicted pancreatic adenocarcinoma signaling as one of the most significantly affected canonical pathway upon MYB-silencing. Altogether, our findings identify novel MYB-regulated gene networks and signaling pathways in PC and thus suggest potential molecular mechanisms involved in mediating MYB action in pancreatic tumorigenesis. Citation Format: Shafquat Azim, Sanjeev K. Srivastava, Arun Bhardwaj, Haseeb Zubair, Mohammad Aslam Khan, Seema Singh, Ajay P. Singh. Myb-regulated gene networks and signaling pathways in pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1519.