单位：[a]Department of Pathology Center, Shanghai General Hospital/Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China[b]Cancer institute, Fudan University, Shanghai Cancer Center, Shanghai, China[c]Department of Neurology, Beijing Friendship Hospital, Capital University of Medical Sciences, China临床科室神经内科神经内科首都医科大学附属北京友谊医院[d]Department of Biochemistry and Molecular and Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China[e]National Institute of Biological Sciences (NIBS), Beijing, China[f]School of Medicine, Anhui University of Science & Technology, Huainan, Anhui, China.
Lung cancer is a leading cause of cancer mortality worldwide with dramatically increasing incidence in recent years. However, the mechanism underlying its progression remains unclear. The aim of this study was to identify the role of hypermethylated in cancer 1 (HIC1) in lung cancer development. Here we found that HIC1 expression was markedly decreased in lung cancer compared with the corresponding adjacent non-cancerous tissues. Meanwhile, overall survival (OS) of lung cancer patients was negatively related with HIC1 expression using TCGA and GEO datasets. Loss of HIC1 expression promoted cell proliferation and migration in vitro. Notable, HIC1 knock-out in Kras(G12D/+(Lox-stop-Lox))/sgHIC1 mice had remarkable effect on tumorigenesis compared with Krasc(G12D/+(Lox-stop-Lox))/sgTd control mice. Mechanistic analyses showed that ADAMTS9, DCDC2, FAM46C, ZNF883, F2R, MSH6 and PAX2 genes may be potential downstream targets; DNA repair pathway and transcriptional regulation by TP53 pathway were involved. Finally, this study reveals that HIC1 is associated with lung cancer progression and may provide an effective strategy for its treatment.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772806, 81272404]; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning
第一作者单位：[a]Department of Pathology Center, Shanghai General Hospital/Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[b]Cancer institute, Fudan University, Shanghai Cancer Center, Shanghai, China[f]School of Medicine, Anhui University of Science & Technology, Huainan, Anhui, China.[*1]Cancer institute, Fudan University Shanghai Cancer Center, 200032, China.
推荐引用方式(GB/T 7714)：
Yue Li,Mengfei Yao,Tianqi Wu,et al.Loss of hypermethylated in cancer 1 (HIC1) promotes lung cancer progression[J].CELLULAR SIGNALLING.2019,53:162-169.doi:10.1016/j.cellsig.2018.10.006.
APA：
Yue Li,Mengfei Yao,Tianqi Wu,Liyan Zhang,Yingying Wang...&Jianhua Wang.(2019).Loss of hypermethylated in cancer 1 (HIC1) promotes lung cancer progression.CELLULAR SIGNALLING,53,
MLA：
Yue Li,et al."Loss of hypermethylated in cancer 1 (HIC1) promotes lung cancer progression".CELLULAR SIGNALLING 53.(2019):162-169
