title: JMJD1A promotes tumorigenesis and forms a feedback loop with EZH2/let-7c in NSCLC cells.
abstract: Lung cancer is the most common cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) accounts for 80 to 85 % of all lung cancer. Although the standard treatment regimen has been established, long-term survival for NSCLC patients is still generally poor. The histone demethylase Jumonji domain containing 1A (JMJD1A) has been proposed as an oncogene in several types of human cancer, but its clinical significance and functional roles in NSCLC remain largely unclear. In the present study, JMJD1A was frequently upregulated in NSCLC compared with para-carcinoma tissues. JMJD1A knockdown significantly inhibited NSCLC cell growth, migration, and invasion in vitro and tumorigenesis in vivo. Further experiments demonstrated that JMJD1A knockdown could decrease the expression of EZH2, which has been shown to play a crucial role in the carcinogenesis of NSCLC and, in turn, increase the expression of anti-tumor microRNA let-7c. Also, let-7c directly targeted the 3'-untranslated regions of JMJD1A and EZH2. Taken together, JMJD1A could promote NSCLC tumorigenesis. JMJD1A/EZH2/let-7c constituted a feedback loop and might represent a promising therapeutic target for NSCLC.
authors.affiliation: Shen Zhen Children's Hospital, Shenzhen, 510038, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhan
authors.affiliation: Shen Zhen Children's Hospital, Shenzhen, 510038, People's Republic of China.
authors.forename: Feiqiu
authors.initials: F
authors.lastname: Wen
authors.affiliation: Jiangxi Provincial Cancer Hospital, Nanchang, 330029, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Shen Zhen Children's Hospital, Shenzhen, 510038, People's Republic of China.
authors.forename: Zebin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Shen Zhen Children's Hospital, Shenzhen, 510038, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People's Republic of China. hhzhou2003@163.com.|Institute of Clinical Pharmacology, Central South University, Changsha, 410008, People's Republic of China. hhzhou2003@163.com.|Hunan Key Laboratory of Pharmacogenetics, Changsha, 410008, People's Republic of China. hhzhou2003@163.com.
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism; D016133:Polymerase Chain Reaction; D046888:Tissue Array Analysis
chemical_list: D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D056484:Jumonji Domain-Containing Histone Demethylases; C530247:KDM3A protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: EZH2; Feedback; JMJD1A; Let-7c; NSCLC; Tumorigenesis