Silence of UHRF1 inhibit lung adenocarcinoma proliferation via Wnt/β-catenin signaling pathway

Abstract

Objective To investigate the role and potential mechanism of Ubiquitin like PHD and ring finger domain 1 (UHRF1) in Lung adenocarcinoma. Methods The expression of UHRF1 in lung adenocarcinoma was detected by bioinformatics (TCGA). Real-time quantitative PCR and western blot were used to detect the level of UHRF1 in lung adenocarcinoma cells.The cells in control NC.UHRF1-SiRNA group viability were detected by MTT and colony formation.Ki67 immunofluorescence staining was used to test the proliferation of A549 cells transfected with UHRF1-siRNA or control-siRNA.The proliferation related protein PCNA, Rb, CDK4/6, β-catenin, and GSK-3β in Wnt/β-catenin signaling pathway were determined by Western blotting. Results The expression of UHRF1 in lung adenocarcinoma was higher than that in adjacent tissues(P<0.05). The expression of UHRF1 in 16HBE was lower than that in lung adenocarcinoma cell lines (A549 and H1299) (P<0.05). In addition, MTT and clonogenic assay showed that knocking down UHRF1 could inhibit A549 cell viability(P<0.05). Ki-67 immunofluorescence staining showed that the proliferation of A549 cells decreased after UHRF1 knockdown(P<0.05). In addition, knockdown of UHRF1 decreased the level of PCNA CDK4/6 expression compared with NC group, while the expression of Rb was higer than that of the control group(P<0.05). Knockdown of UHRF1 reduced the expression of β-catenin, while the level of GSK-3β was higher than that in control-siRNA(both P<0.05). Conclusion The UHRF1 may play an important role in the progress of lung adenocarcinoma. Key words: Lung adenocarcinoma; Ubiquitin like PHD and ring finger domain; Proliferation; Wnt