Objective To investigate the effect of microRNA-105-5p(miR-105-5p)on the proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)process of pancreatic cancer PANC-1 cells,focusing on the potential mechanism involving PPM1A.Methods The expression levels of miR-105-5p in human pancreatic duct epithelial cells(hTRET-HPNE)and pancreatic cancer cells(PANC-1,AsPC-1,Bxpc-3)were detected by real-time fluorescence quantitative PCR(qRT-PCR).The relationship between miR-105-5p expression and pancreatic cancer patient prognosis was analyzed using the Kaplan-Meier Plotter online tool.PANC-1 cells were transfected with mimic NC,miR-105-5p mimic,inhibitor NC,and miR-105-5p inhibitor,respectively.Cell proliferation,migration,and invasion were assessed using CCK-8,scratch wound healing,and Transwell assays.The effects of miR-105-5p on the expression of E-cadherin,N-cadherin,Vimentin,and ZEB1 were evaluated by qRT-PCR.Bioinformatics analysis predicted candidate target genes of miR-105-5p,followed by GO and KEGG enrichment analysis.Dual-luciferase reporter assays verified the targeting relationship between miR-105-5p and PPM1A.The expression of PPM1A in PANC-1 cells was detected after transfection with mimic NC,miR-105-5p mimic,inhibitor NC,and miR-105-5p inhibitor.Immunofluorescence experiments were conducted to measure PPM1A expression in hTRET-HPNE and pancreatic cancer cells.Finally,rescue experiments were performed by transfecting PANC-1 cells with mimic NC+pcDNA3.1,mimic NC+pcDNA3.1-PPM1A,miR-105-5p mimic+pcDNA3.1-PPM1A to explore the interaction between miR-105-5p and PPM1A in pancreatic cancer cells.Results The relative expression levels of miR-105-5p mRNA were higher in PANC-1,AsPC-1,and Bxpc-3 cells compared to hTRET-HPNE cells(P＜0.05),with the highest levels in PANC-1 cells.High expression of miR-105-5p was associated with poor prognosis in pancreatic cancer patients(P＜0.05).PANC-1 cells transfected with miR-105-5p mimic showed increased proliferation,migration,and invasion compared to the mimic NC group(P＜0.05).MiR-105-5p mimic decreased E-cadherin mRNA expression and increased N-cadherin,Vimentin,and ZEB1 mRNA expression(P＜0.05),while miR-105-5p inhibitor produced the opposite effects.Dual-luciferase reporter assays confirmed the targeting relationship between miR-105-5p and PPM1A.Immunofluorescence experiments demonstrated lower PPM1A fluorescence intensity in PANC-1,AsPC-1,and Bxpc-3 cells compared to hTRET-HPNE cells(P＜0.05).Rescue experiments indicated that miR-105-5p could partially reverse the inhibitory effects of PPM1A on the proliferation,migration,and invasion of PANC-1 cells(P＜0.05).Conclusion miR-105-5p targets PPM1A to promote the proliferation,migration,and invasion of pancreatic cancer PANC-1 cells.
维普
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