Downregulation of Low-density lipoprotein receptor-related protein 1B (LRP1B) inhibits the progression of hepatocellular carcinoma cells by activating the endoplasmic reticulum stress signaling pathway

Abstract

ABSTRACT Hepatocellular carcinoma (HCC) has a high recurrence rate and mortality rate even after surgery. Low-density lipoprotein receptor-related protein 1B (LRP1B) has proven to be involved in tumor development and progression of multiple malignancies. However, the function of LRP1B in HCC progression has not been fully elucidated. Thus, we conducted this study to explore the relationship between LRP1B and HCC. Bioinformatic analyses implied that LRP1B was highly expressed in HCC tissues. High LRP1B expression was shown to be related to poor outcomes and the determination of HCC patients’ tumor stage. LRP1B deletion impeded the proliferation, migration, and invasion of HCC cells. Further investigation demonstrated that silencing LRP1B expression enhanced the sensitivity of HCC cells to doxorubicin. LRP1B deletion inhibited HCC progression by regulating the PERK-ATF4-CHOP signaling pathway. Additionally, we probed the genomic alterations of LRP1B in HCC and the impact on the prognosis of patients. Collectively, our results suggest that LRP1B plays an essential role in the promotion of HCC progression by regulating the PERK-ATF4-CHOP signaling pathway, which is a potential prognostic biomarker and a promising therapeutic target of HCC.