title: Long non-coding RNA H19 regulates FOXM1 expression by competitively binding endogenous miR-342-3p in gallbladder cancer.
abstract: Long non-coding RNA (lncRNA) H19 has been reported to involve in many kinds of human cancers and functions as an oncogene. Our previous study found that H19 was over-expressed in gallbladder cancer (GBC) and was shown to promote tumor development in GBC. However, the competing endogenous RNA (ceRNA) regulatory network involving H19 in GBC progression has not been fully elucidated. We aim to detect the role of H19 as a ceRNA in GBC.
  
  
  
  In this study, the expression of H19 and miR-342-3p were analyzed in 35 GBC tissues and matched normal tissues by using quantitative polymerase chain reaction (qRT-PCR). We demonstrated H19 was overexpressed and negatively correlated with miR-342-3p in GBC. By dual-luciferase reporter assays, RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays, we verified that H19 was identified as a direct target of miR-342-3p. QRT-PCR and Western-blotting assays demonstrated that H19 silencing down-regulated, whereas over-expression enhanced the expression of miR-342-3p targeting FOXM1 through competitively 'sponging' miR-342-3p. Furthermore, transwell invasion assays and cell cycle assays indicated that H19 knockdown inhibited both cells invasion and proliferation, but this effects was attenuated by co-transfection of siRNA-H19 and miR-342-3p inhibitor in GBC cells. In vivo, tumor volumes were decreased significantly in H19 silenced group compared to the control group, but was attenuated by co-transfection of shRNA-H19 and miR-342-3p inhibitor, which were stablely constructed through lenti-virus vector.
  
  
  
  Our results suggest a potential ceRNA regulatory network involving H19 regulates FOXM1 expression by competitively binding endogenous miR-342-3p in GBC. This mechanism may contribute to a better understanding of GBC pathogenesis and provides potential therapeutic strategy for GBC.
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China.
authors.forename: Shou-Hua
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao tong University School of Medicine, Shanghai, 200092, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China.
authors.forename: Xiao-Cai
authors.initials: XC
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China.
authors.forename: Ming-Di
authors.initials: MD
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China.
authors.forename: Ming-Zhe
authors.initials: MZ
authors.lastname: Weng
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China. wangjiandong228@sina.com.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao tong University School of Medicine, 1665 Kong Jiang Road, Shanghai, 200000, China. Quanzhiwei3@163.com.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Quan
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D000072278:Forkhead Box Protein M1 / Q000235:genetics*; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; C094335:H19 long non-coding RNA; C546176:MIRN342 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding
keywords: Competing endogenous RNA; FOXM1; Gallbladder cancer; H19; miR-342-3p