Abstract 4125: Comparison between knockdown of Pim-1, Pim-2 and Pim-3 identifies Pim-2 as the most relevant Pim oncogene in hepatocellular carcinoma

Abstract Introduction Pim-Kinases (Pim - proviral integration site for moloney murine leukemia virus; Pim-1, -2, -3) are a family of serine/threonine kinases with oncogenic potential. They are overexpressed in various solid tumors including hepatocellular carcinoma (HCC) and have been found responsible for malignant transformation, induction of cell proliferation and inhibition of apoptosis. While the main focus has been on Pim-1 so far, the other Pim kinases, esp. Pim-2, have not been explored in detail. Objectives The aim of this study was to compare the tumor-inhibitory effects of the single and combined of Pim family members in HCC, for evaluating their individual contributions and potential as therapeutic target. To this end, RNA interference (RNAi) for specific gene knockdown was employed. Materials and methods Different HCC cell lines were transfected with small interfering RNAs (siRNAs) for inducing RNAi and transient target gene downregulation. Various cellular and molecular effects were analysed. Results Transient siRNA transfection led to robust and specific knockdown of the selected Pim kinase(s) on mRNA and protein level. This resulted in anti-proliferative and pro-apoptotic effects. Most profound consequences on cell growth, cell cycle and apoptosis were observed upon Pim-2 knockdown, with little additive effects upon combined inhibition. These cellular changes were paralleled by alterations of various genes involved in cell cycle, cell survival, EMT and other important cellular processes. Conclusion In hepatocellular carcinoma, Pim-2 represents a functionally relevant oncogene. We demonstrate its higher potential as compared to the other Pim family members, and analyze various consequences of its inhibition or knockdown on the cellular and molecular level. Taken together, this identifies Pim-2 as a potentially relevant target gene for therapeutic intervention. Citation Format: Ulrike Weirauch, Pia Kürz, Achim M. Aigner. Comparison between knockdown of Pim-1, Pim-2 and Pim-3 identifies Pim-2 as the most relevant Pim oncogene in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4125. doi:10.1158/1538-7445.AM2017-4125