Sigma-1 receptor (σ1R) is downregulated in hepatic malignant tumors and regulates HepG2 cell proliferation, migration and apoptosis

Xu,Qingxia; Li,Liang; Han,Cuihong; Wei,Li; Kong,Lingling; Lin,Fanzhong

doi:10.3892/or.2018.6226

Sigma-1 receptor (σ1R) is downregulated in hepatic malignant tumors and regulates HepG2 cell proliferation, migration and apoptosis

Authors:
- Qingxia Xu
- Liang Li
- Cuihong Han
- Li Wei
- Lingling Kong
- Fanzhong Lin
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Affiliations: Department of Pathology, Jining First People's Hospital, Jining, Shandong 272111, P.R. China, Department of Pathology, Basic Science School, Jining Medical University, Jining, Shandong 272111, P.R. China
Published online on: January 22, 2018 https://doi.org/10.3892/or.2018.6226
Pages: 1405-1413

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Abstract

Sigma-1 receptor (σ1R), an important transmembrane structural protein, has been demonstrated to be overexpressed in various types of human cancer, and has been confirmed to be involved in many biological behaviors during tumorigenesis and tumor progression. The aim of the present study was to explore the essential role of σ1R in hepatic malignant tumors (HMTs), which, to the best of our knowledge, has not been reported to date. We assessed σ1R expression in hepatocellular carcinoma (HCC) tissues and found that σ1R was significantly decreased in HCC when compared with that in benign liver tissues (P<0.01). Additionally, the expression of σ1R was shown to be inversely correlated with HCC grade (r=-0.424, P=0.021, Kendall's τ-b-test). We further used a FLAG‑SV40‑neomycin‑plasmid strategy to increase σ1R expression in the HepG2 hepatoblastoma cell line. Overexpression of σ1R impaired cell proliferation, inhibited cell migration, induced cell cycle arrest at G1 phase, and increased cell apoptosis in vitro. Furthermore, overexpression of σ1R decreased the expression levels of STAT-3 and NF-κB, which provided insight into the underlying mechanisms of σ1R-associated HMT development and progression. These findings suggest that the decreased expression of σ1R plays an essential role in hepatic tumorigenesis, and that it may serve as a potential predictive factor and therapeutic target for the treatment of HMTs.

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