Abstract
p53/p21 signaling plays a vital role in pancreatic cancer (PC) progression. ZWINT was shown to function as an oncoprotein in the progression of multiple cancers. However, the involvement of ZWINT and p53 activation in the progression of PC remains poorly understood. Bioinformatics and tissue array chip analyses were performed to evaluate ZWINT expression in pancreatic cancer. ZWINT mRNA and protein expression were evaluated in normoxia and hypoxia. CHIP was used to evaluate HIF1α interaction with the ZWINT promoter. CCK8, colony formation, EDU, and cell cycle analysis were used to examine PC cell proliferation. Immunoprecipitation and immunofluorescence were used to examine the interaction of ZWINT, MDM2, and p53. p53 activity was evaluated by q-PCR and luciferase assay. Protein degradation and ubiquitination assays were used to analyze the role of ZWINT in p53 ubiquitination. ZWINT was overexpressed in pancreatic cancer and induced in hypoxia. ZWINT promoted pancreatic cancer growth and cell cycle progression. Bioinformatic analysis revealed that ZWINT may regulate the p53 signal pathway. ZWINT interacts with p53 and promotes its ubiquitination and degradation. ZWINT promoted proliferation via p53/p21. Immunohistochemistry of clinical specimens revealed that that ZWINT expression was significantly negatively correlated with p53/p21. Our data showed that hypoxia regulates the expression of ZWINT, which activated p53/p21 signaling pathway to promote PC growth.
Highlights
Pancreatic cancer (PC), one of the most serious gastrointestinal malignancies, is the fourth most frequent cause of cancer-associated death (Siegel et al, 2020)
Together these results indicate that low ZWINT expression is related to progression and poor prognosis in human pancreatic cancer (PC)
We demonstrated that ZWINT, a centromere complex component, was significantly upregulated in PC tumor tissues and high expression of ZWINT was related to poor outcome in PC
Summary
Pancreatic cancer (PC), one of the most serious gastrointestinal malignancies, is the fourth most frequent cause of cancer-associated death (Siegel et al, 2020). Because of the lack of precise diagnostic approaches, PC is usually diagnosed at advanced stage (The Lancet Gastroenterology and Hepatology, 2021). Patients with advanced PC can only receive chemotherapy instead of surgical resection (Perri and Katz, 2021). In the occurrence and development of pancreatic cancer, there are no more accurate early diagnosis and treatment methods. (Lee et al, 2020).
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