JiangSheng Zhao1, GuoFeng Chen1, Jingqi Li2, Shiqi Liu1, Quan Jin1, ZhengWei Zhang2, Fuzhen Qi1, JianHuai Zhang1, JianBo Xu3. 1. Department of Hepatobiliary Surgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huai'an, 223001, Jiangsu, People's Republic of China. 2. Department of Pathology, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huai'an, 223001, Jiangsu, People's Republic of China. 3. Department of Hepatobiliary Surgery, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huai'an, 223001, Jiangsu, People's Republic of China. hayyxjb@njmu.edu.cn.
Abstract
BACKGROUND: PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. METHODS: PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing. RESULTS: PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2. CONCLUSIONS: This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.
BACKGROUND: PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. METHODS: PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing. RESULTS: PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2. CONCLUSIONS: This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.