Transcriptomic changes associated with PCK1 overexpression in hepatocellular carcinoma cells detected by RNA-seq

Jin Xiang; Yuhong Zhang; Lin Tuo; Rui Liu; Dongmei Gou; Li Liang; Chang Chen; Jie Xia; Ni Tang; Kai Wang

doi:10.1016/j.gendis.2019.04.004

Transcriptomic changes associated with PCK1 overexpression in hepatocellular carcinoma cells detected by RNA-seq

Genes Dis. 2019 Apr 16;7(1):150-159. doi: 10.1016/j.gendis.2019.04.004. eCollection 2020 Mar.

Authors

Jin Xiang¹, Yuhong Zhang², Lin Tuo¹, Rui Liu¹, Dongmei Gou¹, Li Liang¹, Chang Chen³, Jie Xia¹, Ni Tang¹, Kai Wang¹

Affiliations

¹ Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
² The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
³ Institute of Life Sciences, Chongqing Medical University, Chongqing, 400010, China.

Abstract

Phosphoenolpyruvate carboxykinase 1 (PCK1), a step limiting enzyme of gluconeogenesis, is downregulated in hepatocellular carcinoma (HCC). Overexpression of PCK1 has been shown to suppress hepatoma cell growth, but the underlying mechanism remains unclear. We used recombinant adenovirus overexpressing PCK1 or GFP in Huh7 cells, and the differentially expressed genes (DEGs) were identified by RNA-Seq. 180 were upregulated by PCK1 overexpression, whereas 316 were downregulated. Pathway analysis illustrated that PCK1 was closely correlated with Wnt signaling pathway and TGF-beta signaling pathway. Hence, Wnt signaling pathway and its downstream component, FZD2, FZD6, FZD7 and β-catenin were confirmed by qRT-PCR and Western blot. In vivo we also observed that PCK1 had restrained tumor growth as a result of decreasing expression of β-catenin. Whole-transcriptomic profile analysis discovered that overexpression of PCK1 downregulates several oncogenic signaling pathways in HCC, providing potential therapeutic targets for improving HCC therapy.

Keywords: Hepatocellular carcinoma cells; Oncogene; Phosphoenolpyruvate carboxylase kinase1 (PCK1); RNA sequencing; Wnt signaling pathway.