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The upregulation of keratocan promotes the progression of human pancreatic cancer
Gao Huijie,Qian Ruikun,Ren Qiang,Zhang Litao,Qin Wei,Zhou Caiju,Wang Huiyun,Liu Chao,Zhang Yuntao 대한독성 유전단백체 학회 2024 Molecular & cellular toxicology Vol.20 No.2
Background The role of the extracellular matrix (ECM) in oncogenic contexts has been studied previously, but the expression patterns and functional role of keratocan, a classical small leucine-rich proteoglycan found in the ECM, in tumors remain poorly understood. As pancreatic cancer (PC) is characterized by desmoplasia in the ECM, this study sought to assess the significance of keratocan in PC. Objective In this study, Gene Expression Profiling Interactive Analysis (GEPIA) was first used to analyze the expression pattern of keratocan in PC. Keratocan, P53, and P21 levels were evaluated in PDAC patient tissues and the role of keratocan was additionally directly assessed via transfecting PDAC cell lines with a pENTER-human keratocan construct. Results Patients with PC showing high levels of keratocan had low survival rates. A significantly upregulated expression of keratocan was observed in the PC tumor tissues in comparison to healthy paracancerous tissues. Keratocan upregulation in BxPC-3 and PANC-1 cells markedly enhanced their proliferation and migration, but reduced cellular apoptosis. Furthermore, the P53 and P21 expression levels were significantly reduced in pancreatic ductal adenocarcinoma cells overexpressing keratocan. P53 and P21 were downregulated in PC tumor tissues. Conclusions All results showed that keratocan played important roles in the promoting of PC. Background The role of the extracellular matrix (ECM) in oncogenic contexts has been studied previously, but the expression patterns and functional role of keratocan, a classical small leucine-rich proteoglycan found in the ECM, in tumors remain poorly understood. As pancreatic cancer (PC) is characterized by desmoplasia in the ECM, this study sought to assess the significance of keratocan in PC. Objective In this study, Gene Expression Profiling Interactive Analysis (GEPIA) was first used to analyze the expression pattern of keratocan in PC. Keratocan, P53, and P21 levels were evaluated in PDAC patient tissues and the role of keratocan was additionally directly assessed via transfecting PDAC cell lines with a pENTER-human keratocan construct. Results Patients with PC showing high levels of keratocan had low survival rates. A significantly upregulated expression of keratocan was observed in the PC tumor tissues in comparison to healthy paracancerous tissues. Keratocan upregulation in BxPC-3 and PANC-1 cells markedly enhanced their proliferation and migration, but reduced cellular apoptosis. Furthermore, the P53 and P21 expression levels were significantly reduced in pancreatic ductal adenocarcinoma cells overexpressing keratocan. P53 and P21 were downregulated in PC tumor tissues. Conclusions All results showed that keratocan played important roles in the promoting of PC.
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