SOD2 promotes the expression of ABCC2 through lncRNA CLCA3p and improves the detoxification capability of liver cells

• DOI: 10.1016/j.toxlet.2020.03.013
• Publication Date: 2020-03-20T01:07:06Z
• Authors: Xiaoqian Wang; Man Li; Lirong Peng; Nanhong Tang
• Keywords: 0303 health sciences; Paclitaxel; Superoxide Dismutase; Antineoplastic Agents, Phytogenic; Multidrug Resistance-Associated Protein 2; 03 medical and health sciences; Gene Expression Regulation; Liver; Cell Line, Tumor; Animals; Humans; RNA Interference; RNA, Long Noncoding; Multidrug Resistance-Associated Proteins; Cell Proliferation; Oligonucleotide Array Sequence Analysis

Superoxide dismutase 2 (SOD2) is a key enzyme for scavenging reactive oxygen species produced by mitochondria, which plays an important role in maintaining cellular homeostasis. However, its effects on the detoxification capability of liver cells have not been reported. In this study, we found that change in SOD2 expression affects the proliferation of liver cells. Genome-wide microarray analysis showed that SOD2 positively regulates the drug transporter ABCC2, and co-expression analysis suggested that lncRNA CLCA3P participates in the process. Further experiments showed that SOD2 can promote the expression of CLCA3P, which increases the transcription of ABCC2 by interacting with the transcription factor IRF1. By increasing ABCC2 expression SOD2 facilitates drugs efflux of liver cells and thus promotes their survival under a drug-toxic environment. This study elucidates the improvement of the detoxification of liver cells by a regulatory axis, SOD2-CLCA3P-IRF1-ABCC2, and provides novel insight into the modification of human liver cells that can be applied to bioartificial liver system or the study of SOD2 in drug metabolism.