OncoTargets and Therapy (Sep 2019)
Silencing stomatin-like protein 2 attenuates tumor progression and inflammatory response through repressing CD14 in liver cancer
Abstract
Xiaolin Pu,1,* Changqing Dong,2,* Wenyu Zhu1, Wei Li3, Hua Jiang1 1Department of Oncology, Changzhou Second People’s Hospital, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Thoracic Surgery, Nanjing Chest Hospital, Nanjing City, Jiangsu Province, People’s Republic of China; 3Department of Oncology, Jiangsu Province People’s Hospital, Nanjing, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua JiangDepartment of Oncology, Changzhou Second People’s Hospital, No. 29 Xinglong Lane, Tianning District, Changzhou, Jiangsu Province 213004, People’s Republic of ChinaTel +86 5 198 810 4931Email [email protected]: Toll-like receptor 4 (TLR4) is involved in the inflammation in liver cancer. High-expressed stomatin-like protein 2 (SLP-2) is commonly reported in many cancer types. This study aims to investigate the functions of SLP-2 in TLR4-mediated inflammatory responses and tumor progression of liver cancer.Patients and methods: Plasmid transfection technique was applied to silence and overexpress genes. Changes in cell viability and apoptosis were determined by performing cell counting kit-8 assay and flow cytometry. The levels of pro-inflammatory cytokines were determined by ELISA. We further measured the several types of the malignant transformation of SK-Hep1 cells to assess the effects of SLP-2 silencing on the cell migration and invasion, proliferation and angiogenesis of liver cancer in vitro. Western blot and RT-qPCR were performed for expression analysis.Results: Lipopolysaccharide (LPS) promoted the cell proliferation of SK-Hep1 and production of tumor necrosis factor-α (TNF-α) and IL-6. SLP-2 silencing could inhibit the protein and mRNA levels of CD14 and Cdc42 and subsequently inhibited the levels of TNF-α and IL-6. Overexpressed CD14 not only remarkably reversed the proapoptotic ability of SLP-2 silencing and promoted the expression of Cdc42 and production of TNF-α and IL-6, but also notably reversed the inhibitory effects on the malignant abilities of SK-Hep1 cells by SLP-2 silencing.Conclusion: SLP-2 silencing could significantly attenuate the inflammatory responses and tumor progression of liver cancer via inhibiting LPS/TLR4 signal transduction through the repression of CD14.Keywords: liver cancer, stomatin-like protein 2, Toll-like receptor 4, apoptosis, inflammatory response
