Tankyrase 2 promotes lung cancer cell malignancy  

作　　者：Ying Wang Yong-Jun Zhang 

机构地区：[1]Department of Gynecological Oncology,Zhejiang Cancer Hospital,Hangzhou 310022,Zhejiang Province,China [2]Department of Integrated Traditional Chinese and Western Medicine,Zhejiang Cancer Hospital,Hangzhou 310022,Zhejiang Province,China

出　　处：《World Journal of Clinical Oncology》2024年第6期755-764,共10页世界临床肿瘤学杂志（英文版）

基　　金：Supported by Traditional Chinese Medicine Foundation of Zhejiang Province,No.2019ZA020。

摘　　要：BACKGROUND Tankyrase 2(TNKS2)is a potential candidate molecular target for the prognosis and treatment of non-small cell lung cancer(NSCLC),but its biological functions are unclear.AIM To investigate the biological functions of TNKS2 in NSCLC.METHODS Using a lentiviral vector,we generated H647 model cells with TNKS2 knockdown by RNA interference and A549 model cells with TNKS2 overexpression by tran-sfection with a TNKS2 overexpressing plasmid.Increased and decreased exp-ression levels of TNKS2 in the two cell lines were verified using real-time reverse transcriptase-polymerase chain reaction and Western blot analyses.Cell apopto-sis,proliferation,and migration were determined using flow cytometry,carbo-xyfluorescein succinimidyl ester staining,and scratch assay,respectively.Im-munofluorescence staining was conducted to examine TNKS2 andβ-catenin ex-pression levels in the two transfected cell lines and the non-transfected cells.RESULTS TNKS2 mRNA and protein expression was significantly higher in the highly malignant NCI-H647 cells,while it remained at a low level in the less malignant A549 cells.Lentivirus-mediated overexpression of TNKS2 in A549 cells resulted in a 3-fold increase in gene expression and a 1.7-fold increase in protein expression(P<0.01).Conversely,shRNA interference targeting TNKS2 Led to an 8-fold decrease in gene expression and a 3-fold decrease in protein expression(P<0.01)in NCI-H647 cells.Furthermore,the cell apoptosis rate was significantly reduced(50%)and cell migration rate was increased(35%)in the TNKS2 overexpression group than in the control group(P<0.05).In contrast,shTNKS2 promoted apoptosis by more than one fold and reduced migration by 60%(P<0.05).Immunofluorescence analysis revealed enhanced nuclear localization ofβ-catenin fluorescence signal associated with high TNKS2 expression levels.Western blot analysis investigating TNKS2/β-catenin-related proteins indicated consistent changes between TNKS2 andβ-catenin expression in lung cancer cells,whereas Axin displayed an opposite

关 键 词：Apoptosis MIGRATION Lung Cancer PROLIFERATION Tankyrase 2 

分 类 号：R73[医药卫生—肿瘤]