Protein phosphatase 2 regulatory subunit B''Alpha silencing inhibits tumor cell proliferation in liver cancer
CANCER MEDICINE(2019)
Abstract
Aim To explore the effects of protein phosphatase 2 regulatory subunit B"Alpha (PPP2R3A) on the proliferation and migration of liver cancer cells. Methods Expression of PPP2R3A in tumor tissues of hepatocellular carcinoma (HCC) patients was detected by immunohistochemistry and western blotting. In two liver cancer cell lines (HepG2 and HuH7), PPP2R3A expression was silenced and then overexpression with PPP2R3A lentiviral vectors, and the effects of PPP2R3A knockdown or overexpression on the proliferation, cell cycle, migration, and invasion of HCC cells were determined in vitro. In a xenograft cancer model in nude mice, the in vivo effects of PPP2R3A knockdown on tumor growth and cancer cell proliferation were evaluated. Results PPP2R3A expression was found in tumor foci in six of eight HCC samples, at a level higher than that in the adjacent para-tumor tissues. PPP2R3A expression was observed primarily in the cytoplasm of the cancer cells. Knockdown of PPP2R3A resulted in significant inhibition of hepatoma cell proliferation (P < .05), migration (P < .01), and invasion (P < .01) as well as a significant delay in the G1/S transition in both liver cancer lines (P < .05) and increased p53 expression. Conversely, overexpression of PPP2R3A promoted the proliferation (P < .05) and altered cell cycle progression (P < .05) of both liver cancer cell lines. In vivo, PPP2R3A knockdown in liver cancer cells led to significant reductions in the tumor volume (P < .001) and the expression of Ki-67 in tumor tissues (P < .05). Conclusion PPP2R3A may play a role in liver cancer via the regulation of tumor cell proliferation and invasion.
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Key words
liver cancer,migration,proliferation
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