RACK1 promotes hepatocellular carcinoma cell survival via CBR1 by suppressing TNF-α-induced ROS generation

Zhou,Silei; Cao,Huanling; Zhao,Yawei; Li,Xinying; Zhang,Jiyan; Hou,Chunmei; Ma,Yuanfang; Wang,Qingyang

doi:10.3892/ol.2016.5339

RACK1 promotes hepatocellular carcinoma cell survival via CBR1 by suppressing TNF-α-induced ROS generation

Authors:
- Silei Zhou
- Huanling Cao
- Yawei Zhao
- Xinying Li
- Jiyan Zhang
- Chunmei Hou
- Yuanfang Ma
- Qingyang Wang
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Affiliations: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China, Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan 475004, P.R. China
Published online on: November 2, 2016 https://doi.org/10.3892/ol.2016.5339
Pages: 5303-5308

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Abstract

It has been reported that intracellular accumulation of reactive oxygen species (ROS) has a significant role in tumor necrosis factor (TNF)-α-induced cell apoptosis and necrosis; however, the key molecules regulating ROS generation remain to be elucidated. The present study reports that knockdown of endogenous receptor for activated C kinase 1 (RACK1) increases the intracellular ROS level following TNF‑α or H2O2 stimulation in human hepatocellular carcinoma (HCC) cells, leading to promotion of cell death. Carbonyl reductase 1 (CBR1), a ubiquitous nicotinamide adenine dinucleotide phosphate‑dependent enzyme, is reported to protect cells from ROS‑induced cell damage. The present study reports that RACK1 is a regulator of CBR1 that interacts with and sustains the protein stability of CBR1. Overexpression of CBR1 reverses the enhanced cell death due to RACK1 knockdown. Taken together, the results of the present study suggest that RACK1 protects HCC cells from TNF‑α‑induced cell death by suppressing ROS generation through interacting with and regulating CBR1.

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