Background:Pancreatic ductal adenocarcinoma(PDAC)poses a serious threat to human health with high mortality and poor prognosis,and there is an urgent need to explore the pathogenesis of PDAC in order to search for new...Background:Pancreatic ductal adenocarcinoma(PDAC)poses a serious threat to human health with high mortality and poor prognosis,and there is an urgent need to explore the pathogenesis of PDAC in order to search for new therapeutic targets.Methods:The expression of lamininγ-2(LAMC2)in PDAC and its effect on the prognosis of tumor patients were predicted by an online database,and the expression level of LAMC2 in pancreatic cancer was verified by polymerase chain reaction(PCR)and western blot;flow cytometry,wound healing assay,Cell counting kit-8(CCK8)assay,and colony formation assay were used to explore the effect of LAMC2 on the proliferation and migration of pancreatic cancer cells;and we also probed the potential relationship between LAMC2 and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling.Results:High levels of LAMC2 in pancreatic cancer may benefit tumor proliferation migration and invasion and lead to poor prognosis of tumor patients.The mechanism by which LAMC2 promotes PDAC progression may be related to the activation of PI3K/Akt signaling to influence apoptosis and cell cycle.Conclusions:LAMC2 promotes proliferation migration invasion of PDAC and leads to poor prognosis in pancreatic cancer patients.展开更多
Background:Cell competition is an important feature in pancreatic cancer(PC)progression,but the underlying mechanism remains elusive.This study aims to explore the role of exosomes derived from normal pancreatic ducta...Background:Cell competition is an important feature in pancreatic cancer(PC)progression,but the underlying mechanism remains elusive.This study aims to explore the role of exosomes derived from normal pancreatic ductal epithelial cells involved in PC progression.Methods:PC cells and pancreatic stellate cells(PSCs)were treated with exosomes isolated from pancreatic ductal epithelial cells.Cell proliferation was assessed by CCK8 assays.Cell migration and invasion were assessed by Transwell assays.PC and matched adjacent non-tumor tissue specimens were obtained from 46 patients pathologically diagnosed with PC at Peking University First Hospital from 2013 to 2017.Tissue miR-485-3p and p21-activated kinase-1(PAK1)expression was examined by real-time polymerase chain reaction(RT-PCR),and the relationship of the two was analyzed using Pearman’s product-moment correlation.The clinical significance of miR-485-3p was analyzed using the Chi-square test,Wilcoxon rank-sum test,and Fisher exact probability,respectively.The binding of miR-485-3p to PAK15’-untranslated region(5’-UTR)was examined by luciferase assay.PC cells were xenografted into nude mice as a PC metastasis model.Results:Exosomes from pancreatic ductal epithelial cells suppressed PC cell migration and invasion as well as the secretion and migration of PSCs.MiR-485-3p was enriched in the exosomes of pancreatic ductal epithelial cells but deficient in those of PC cells and PSCs,in accordance with the lower level in PSCs and PC cells than that in pancreatic ductal cells.And the mature miR-485-3p could be delivered into these cells by the exosomes secreted by normal pancreatic duct cells,to inhibit PC cell migration and invasion.Clinical data analysis showed that miR-485-3p was significantly decreased in PC tissues(P<0.05)and was negatively associated with lymphovascular invasion(P=0.044).As a direct target of miR-485-3p,PAK1 was found to exert an inhibitory effect on PC cells,and there was a significantly negative correlation between the expression levels of miR-485-3p and PAK1(r=-0.6525,P<0.0001)in PC tissues.Moreover,miR-485-3p could suppress PC metastasisin vivo by targeting p21-activated kinase-1.Conclusions:Exosomal miR-485-3p delivered by normal pancreatic ductal epithelial cells into PC cells inhibits PC metastasis by directly targeting PAK1.The restoration of miR-485-3p by exosomes or some other vehicle might be a novel approach for PC treatment.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.82171722,82271764,81871954)Beijing Municipal Natural Science Foundation(No.7212111).
文摘Background:Pancreatic ductal adenocarcinoma(PDAC)poses a serious threat to human health with high mortality and poor prognosis,and there is an urgent need to explore the pathogenesis of PDAC in order to search for new therapeutic targets.Methods:The expression of lamininγ-2(LAMC2)in PDAC and its effect on the prognosis of tumor patients were predicted by an online database,and the expression level of LAMC2 in pancreatic cancer was verified by polymerase chain reaction(PCR)and western blot;flow cytometry,wound healing assay,Cell counting kit-8(CCK8)assay,and colony formation assay were used to explore the effect of LAMC2 on the proliferation and migration of pancreatic cancer cells;and we also probed the potential relationship between LAMC2 and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling.Results:High levels of LAMC2 in pancreatic cancer may benefit tumor proliferation migration and invasion and lead to poor prognosis of tumor patients.The mechanism by which LAMC2 promotes PDAC progression may be related to the activation of PI3K/Akt signaling to influence apoptosis and cell cycle.Conclusions:LAMC2 promotes proliferation migration invasion of PDAC and leads to poor prognosis in pancreatic cancer patients.
基金National Natural Science Foundation of China(No.82171722,No.81871954)the Beijing Natural Science Foundation(No.7212111)the Peking University Medicine Fund of Fostering Young Scholar’s Scientific&Technological Innovation supported by"the Fundamental Research Funds for the Central Universities"(BMU2018PY026)。
文摘Background:Cell competition is an important feature in pancreatic cancer(PC)progression,but the underlying mechanism remains elusive.This study aims to explore the role of exosomes derived from normal pancreatic ductal epithelial cells involved in PC progression.Methods:PC cells and pancreatic stellate cells(PSCs)were treated with exosomes isolated from pancreatic ductal epithelial cells.Cell proliferation was assessed by CCK8 assays.Cell migration and invasion were assessed by Transwell assays.PC and matched adjacent non-tumor tissue specimens were obtained from 46 patients pathologically diagnosed with PC at Peking University First Hospital from 2013 to 2017.Tissue miR-485-3p and p21-activated kinase-1(PAK1)expression was examined by real-time polymerase chain reaction(RT-PCR),and the relationship of the two was analyzed using Pearman’s product-moment correlation.The clinical significance of miR-485-3p was analyzed using the Chi-square test,Wilcoxon rank-sum test,and Fisher exact probability,respectively.The binding of miR-485-3p to PAK15’-untranslated region(5’-UTR)was examined by luciferase assay.PC cells were xenografted into nude mice as a PC metastasis model.Results:Exosomes from pancreatic ductal epithelial cells suppressed PC cell migration and invasion as well as the secretion and migration of PSCs.MiR-485-3p was enriched in the exosomes of pancreatic ductal epithelial cells but deficient in those of PC cells and PSCs,in accordance with the lower level in PSCs and PC cells than that in pancreatic ductal cells.And the mature miR-485-3p could be delivered into these cells by the exosomes secreted by normal pancreatic duct cells,to inhibit PC cell migration and invasion.Clinical data analysis showed that miR-485-3p was significantly decreased in PC tissues(P<0.05)and was negatively associated with lymphovascular invasion(P=0.044).As a direct target of miR-485-3p,PAK1 was found to exert an inhibitory effect on PC cells,and there was a significantly negative correlation between the expression levels of miR-485-3p and PAK1(r=-0.6525,P<0.0001)in PC tissues.Moreover,miR-485-3p could suppress PC metastasisin vivo by targeting p21-activated kinase-1.Conclusions:Exosomal miR-485-3p delivered by normal pancreatic ductal epithelial cells into PC cells inhibits PC metastasis by directly targeting PAK1.The restoration of miR-485-3p by exosomes or some other vehicle might be a novel approach for PC treatment.
