Y-box binding protein 1 augments sorafenib resistance <i>via</i> the PI3K/Akt signaling pathway in hepatocellular carcinoma
Ting Liu, Xiao‐Li Xie, Xue Zhou, Shengxiong Chen, Yijun Wang, Linping Shi, Shu-Jia Chen, Yongjuan Wang, Shuling Wang, Jiu-Na Zhang, Shiying Dou, Xiaoyu Jiang, Ruolin Cui, Huiqing Jiang
Abstract
BACKGROUND: Sorafenib is the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). Y-box binding protein 1 (YB-1) is closely correlated with tumors and drug resistance. However, the relationship between YB-1 and sorafenib resistance and the underlying mechanism in HCC remain unknown. AIM: To explore the role and related mechanisms of YB-1 in mediating sorafenib resistance in HCC. METHODS: . Moreover, we studied and verified the specific molecular mechanism of YB-1 mediating sorafenib resistance in hepatoma cells by digital gene expression sequencing (DGE-seq). RESULTS: was enhanced after YB-1 was knocked down. Furthermore, KEGG pathway enrichment analysis of DGE-seq demonstrated that the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was essential for the sorafenib resistance induced by YB-1. Subsequently, YB-1 interacted with two key proteins of the PI3K/Akt signaling pathway (Akt1 and PIK3R1) as shown by searching the BioGRID and HitPredict websites. Finally, YB-1 suppressed the inactivation of the PI3K/Akt signaling pathway induced by sorafenib, and the blockade of the PI3K/Akt signaling pathway by LY294002 mitigated YB-1-induced sorafenib resistance. CONCLUSION: Overall, we concluded that YB-1 augments sorafenib resistance through the PI3K/Akt signaling pathway in HCC and suggest that YB-1 is a key drug resistance-related gene, which is of great significance for the application of sorafenib in advanced-stage HCC.