title: Upregulation of H19 indicates a poor prognosis in gallbladder carcinoma and promotes epithelial-mesenchymal transition.
abstract: The imprinted oncofetal long non-coding RNA H19 has been reported to be involved in many kinds of human cancers. However, whether lncRNA H19 implicate in oncogenesis and cancer progression in gallbladder cancer remain largely unknown. In the present study, compared with adjacent normal tissues, the level of H19 was significantly upregulated in gallbladder cancer tissues and was positively associated with lymphatic metastasis and tumor size. The overall survival is shorter in those who had higher H19 expression among GBC patients. In vitro, both TGF-β1 and IL-6 treatment induced upregulation of H19, downregulated the protein level of E-cadherin while increased Vimentin, indicating an epithelial-mesenchymal transition (EMT) phenotype in GBC. The overexpression of H19 in GBC cells enhanced tumor invasion and promoted EMT by upregulated transcription factor Twist1. On the contrary, Loss of function studies indicated that H19 interference in GBC suppressed tumor cell invasion and promoted mesenchymal-epithelial transition (MET) via suppressing Twist expression. In vivo, the volume of the tumors in H19-inteference group was significantly decreased compared to those in the control group of nude mice. Both western-blot and immunohistochemistry confirmed that a MET phenotype existed in the H19 interference group when compared to control group. These results defined H19 as a novel prognostic factor for GBC, and indicated that it might play important regulatory roles in the EMT process.
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200000, China.
authors.forename: Shou-Hua
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine 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 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 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 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 Shanghai 200000, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Quan
keywords: Gallbladder cancer; H19; epithelial-mesenchymal transition; tumor invasion