Protein phosphatase 2 regulatory subunit B''Alpha silencing inhibits tumor cell proliferation in liver cancer

Abstract

AimTo explore the effects of protein phosphatase 2 regulatory subunit B''Alpha (PPP2R3A) on the proliferation and migration of liver cancer cells.MethodsExpression 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.ResultsPPP2R3A 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).ConclusionPPP2R3A may play a role in liver cancer via the regulation of tumor cell proliferation and invasion.

Chitosan oligosaccharides packaged into rat adipose mesenchymal stem cells-derived extracellular vesicles facilitating cartilage injury repair and alleviating osteoarthritis

“…BAD plays a key role in mitochondria-dependent apoptosis, and its inactivation contributes to the development of rheumatoid arthritis by conferring apoptosis resistance in synovial sub lining macrophages [ 58 ]. PPP2R3A , a major serine/threonine phosphatase, is involved in a variety of cellular processes, including cell apoptosis, proliferation, DNA repair, and autophagy [ 59 ], and its knockdown inhibits the proliferation, migration, and invasion of hepatoma carcinoma cells [ 60 ]. CPT1B and ACACB are genes related to fatty acid oxidation [ 61 ] and are associated with obesity and diabetes.…”

High expression of protein phosphatase 2 regulatory subunit B'' alpha predicts poor outcome in hepatocellular carcinoma patients after liver transplantation

“…Therefore, the cytoplasm and cell membrane are key components of the biological function of this gene[ 25 ]. Our previous research using Western blot also showed that PPP2R3A protein in HCC tissue had higher expression compared to the corresponding adjacent tissue[ 26 ]. Thus, the overexpression of PPP2R3A might be related to the malignant biological behavior of HCC, contributing to the occurrence and development of HCC.…”

“…It was previously reported that more than 95% of HCC had an abnormal Wnt/β-catenin signaling pathway[ 41 ], with the upregulation of β-catenin promoting the proliferation and migration capabilities of HCC cells. Our group also previously demonstrated that the PPP2R3A gene promotes the proliferation and invasion of HCC cells by regulating the expression of p53 and β-catenin protein and inhibiting HCC cell apoptosis through the caspase apoptosis pathway[ 25 , 26 ]. After PPP2R3A is overexpressed, spliced PARP expression decreased in cells, with PARP protein representing a universal marker for promoting cell apoptosis, while PARP-1 is related to the tumor stage of liver cancer[ 25 ].…”

“…We previously demonstrated that the overexpression of PPP2R3A promotes the proliferation of HCC cells and, potentially, the invasion and migration of HCC cells. The down-regulation of PPP2R3A gene expression could inhibit the proliferation of HCC cells[ 25 , 26 ]. However, the relationship between the PPP2R3A gene and prognosis of HCC patients after LT remains unclarified, along with the prognostic value of PPP2R3A .…”

Expression Profile Analysis to Identify Circular RNA Expression Signatures in Muscle Development of Wu'an Goat Longissimus Dorsi Tissues

“…Protein phosphatase 2 regulatory subunit B″α ( PPP2R3A ) has been found to regulate the Wnt signaling cascade and 5′adenosine monophosphate-activated protein kinase (AMPK) activity, which have functions such as enhancing cell proliferation and migration ( 57 , 58 ). Some researchers have performed transcriptome sequencing on the longissimus dorsi muscles of different breeds and identified the differentially expressed circRNA host gene PPP2R3A ( 21 ), and Chen et al found that knocking out PPP2R3A could significantly inhibit the proliferation of liver cancer cells, while the overexpression of PPP2R3A promoted the proliferation of two liver cancer cell lines ( 59 ). The source genes of these circRNAs (novel_circ_0005314, novel_circ_0005319, novel_circ_0009256, novel_circ_0009845, novel_circ_0005934 and novel_circ_0000134) might be involved in regulating the growth and development of muscle cells, whose specific functions require further investigation.…”