12 November 2018 : Laboratory Research
Up-Regulation of Phosphatase in Regenerating Liver-3 (PRL-3) Contributes to Malignant Progression of Hepatocellular Carcinoma by Activating Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Phosphoinositide 3-Kinase (PI3K)/AKT Signaling PathwayBing-Hui Li1CDE, Yang Wang1DE, Chao-Yang Wang1EF, Ming-Juan Zhao2F, Tong Deng1BCD, Xue-Qun Ren1AB*
Med Sci Monit 2018; 24: LBR8105-8114
BACKGROUND: The purpose of the study was to investigate the functional roles of phosphatase in regenerating liver-3 (PRL-3) in hepatocellular carcinoma (HCC), as well as the related molecular mechanisms.
MATERIAL AND METHODS: HCC tissues and adjacent normal tissues were collected from 124 HCC patients. The mRNA and protein levels of PRL-3 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, respectively. The relationship between PRL-3 expression and clinical characteristics of HCC patients was evaluated by chi-square test. MTT and Transwell assays were performed to estimate cell proliferation and motility, respectively.
RESULTS: The expression of PRL-3 was significantly increased in HCC tissues and cells at both protein and mRNA levels (P<0.01 for all). Furthermore, the up-regulation of PRL-3 was positively correlated with hepatic vascular invasion (P=0.019), lymph node metastasis (P=0.012), and TNM stage (P=0.001). The knockdown of PRL-3 suppressed HCC cell proliferation, migration, and invasion, and PR3K/AKT pathway activity was also obviously inhibited in HCC cells with PRL-3 deficiency. The levels of PTEN were negatively associated with PRL-3 expression. PRL-3 might inhibit the protein level of PTEN through enhancing its phosphorylation level. The transfection of si-PTEN can reverse the anti-tumor action caused by PRL-3 knockdown in HCC cells.
CONCLUSIONS: Up-regulation of PRL-3 may activate the PI3K/AKT signaling pathway and enhance malignant progression of HCC through targeting PTEN.
Keywords: Acid Phosphatase, PTEN Phosphohydrolase
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