LncRNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 and predicts poor prognosis in lung cancer patients  

作　　者：Haihua Tian Jinchang Pan Shuai Fang Chengwei Zhou Hui Tian Jinxian He Weiyu Shen Xiaodan Meng Xiaofeng Jin Zhaohui Gong 

机构地区：[1]Department of Biochemistry and Molecular Biology,Ningbo University School of Medicine,Ningbo 315211,China [2]Zhejiang Province Key Laboratory of Pathophysiology,Ningbo University School of Medicine,Ningbo 315211,China [3]Department of Thoracic Surgery,The Affiliated Hospital of Ningbo University School of Medicine,Ningbo 315020,China [4]Department of Thoracic Surgery,The Affiliated Lihuili Hospital of Ningbo University,Ningbo 315048,China

出　　处：《Cancer Biology & Medicine》2021年第3期675-692,共18页癌症生物学与医学（英文版）

基　　金：supported in part by research grants from the Non-profit Technology Research Program of Zhejiang(Grant No.LGF18H160006);the Natural Science Foundation of Zhejiang(Grant No.LQ18H200001);the Non-profit Technology Research Program of Ningbo(Grant No.2019C50040);the Natural Science Foundation of Ningbo(Grant No.2018A610204);the Major Project for Science and Technology Innovation 2025 of Ningbo(Grant No.2019B10037);the K.C.Wong Magna Fund at Ningbo University。

摘　　要：Objective:The purpose of this study was to explore the function and gene expression regulation of the newly identified lnc RNA DPP10-AS1 in lung cancer,and its potential value as a prognostic biomarker.Methods:q RT-PCR and Western blot were conducted to detect the expression of DDP10-AS1 and DPP10 in lung cancer cell lines and tissues.The effects of DDP10-AS1 on DPP10 expression,cell growth,invasion,apoptosis,and in vivo tumor growth were investigated in lung cancer cells by Western blot,rescue experiments,colony formation,flow cytometry,and xenograft animal experiments.Results:The novel antisense lnc RNA DPP10-AS1 was found to be highly expressed in cancer tissues(P<0.0001),and its upregulation predicted poor prognosis in patients with lung cancer(P=0.0025).Notably,DPP10-AS1 promoted lung cancer cell growth,colony formation,and cell cycle progression,and repressed apoptosis in lung cancer cells by upregulating DPP10 expression.Additionally,DPP10-AS1 facilitated lung tumor growth via upregulation of DPP10 protein in a xenograft mouse model.Importantly,DPP10-AS1 positively regulated DPP10 gene expression,and both were coordinately upregulated in lung cancer tissues.Mechanically,DPP10-AS1 was found to associate with DPP10 m RNA but did not enhance DPP10 m RNA stability.Hypomethylation of DPP10-AS1 and DPP10 contributed to their coordinate upregulation in lung cancer.Conclusions:These findings indicated that the upregulation of the antisense lnc RNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene DPP10.DPP10-AS1 may serve as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.

关 键 词：Antisense long noncoding RNA DPP10-AS1 HYPOMETHYLATION malignant process lung cancer 

分 类 号：R734.2[医药卫生—肿瘤]