Effect of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in pancreatic cancer

Abstract

Pancreatic cancer (PC) is a serious malignancy with high mortality and poor prognosis due to nonspecific incipient symptoms and early metastasis. Also, increasing evidence indicates that a panel of genes is newly identified in the pathogenesis of PC. As is a regulatory subunit, elevated cyclin B1 (CCNB1) expression has been detected in different cancers including PC. This study is designed to investigate the effects of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in PC. PC tissues and normal pancreatic tissues were collected. Cells were transfected and assigned into different groups. The expressions of CCNB1, p53, MDM2, Bax, caspase-9, caspase-3, and p21 in tissues and cells were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. β-Galactosidase staining, MTT assay, and flow cytometry were conducted to test cell senescence, proliferation, cell cycle, and apoptosis. PC tissues showed higher expressions of CCNB1 and MDM2 and lower expressions of Bax, caspase-9, caspase-3, and p21. Cells transfected with shCCNB1 had lower expressions of CCNB1 and MDM2, whereas higher expressions of Bax, caspase-9, caspase-3, p53, and p21. The shCCNB1 group had decreased proliferation and S-phase cell proportion and increased apoptosis, senescence, and G0/G1-phase cell proportion. The PFT-α group showed higher expressions of MDM2 and lower expressions of Bax, caspase-9, caspase-3, p53, and p21. The PFT-α group had increased proliferation and S-phase cell proportion and declined apoptosis, senescence, and G0/G1-phase cell proportion. CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in PC.

LINC00346 Acts as a Competing Endogenous RNA Regulating Development of Hepatocellular Carcinoma via Modulating CDK1/CCNB1 Axis

“…In exploring the specific molecular mechanism of CDK1/CCNB1 in regulating cancer, Zhang et al revealed that CCNB1 could affect the cell cycle and apoptosis of pancreatic cancer cells by regulating p53 signaling pathway (Zhang H. et al, 2018). Qin G et al reported that the p53 signaling pathway may be regulated by multiple genes to affect the development of liver cells (Qin et al, 2019).…”

Identification of Novel Hub Genes Associated With Gastric Cancer Using Integrated Bioinformatics Analysis

“…Previous studies have reported that the CCNB1-Cdk1 complex is a key regulator of mitotic entry [21]. Recently, increasing evidence demonstrated that CCNB1 was over-expressed in considerable cancers with poor prognosis, including hepatocellular carcinoma [22,23], breast Cancer [24,25], and pancreatic cancer [26,27].The expression of CCNB1 is often used to estimate prognosis after treatment with anticancer drugs [22,28].…”

Screening of significant biomarkers with poor prognosis in hepatocellular carcinoma via bioinformatics analysis

“…[ 23 , 24 ] However, in most tumors, p53 gene is inactivated by mutation or degradation of its associated pathway. [ 24 ] Zhang et al [ 25 ] have demonstrated that CCNB1 silencing could suppress pancreatic cancer cell proliferation and promote apoptosis through activating the p53 signaling pathway. Chai et al [ 26 ] have reported that FOXM1 could promote proliferation of HCC cells via transcriptional activation of CCNB1.…”