Hotair Mediates Hepatocarcinogenesis through Suppressing MiRNA-218 Expression and Activating XXXX and @entity986 Signaling.

@entity1 @entity986 @entity5 @entity19 @entity3752 @entity157
BACKGROUND _ AIMS: Long noncoding RNA Hotair has been considered as a pro-oncogene in multiple @entity5 . Although there is a group of emerging evidence which reveals its biological function and the association with clinical prognosis, the precise mechanism remains largely elusive. METHODS: We investigated the function and mechanism of Hotair in @entity157 ( @entity157 ) cell models and a xenograft @entity19 model. The regulatory network between miR-218 and Hotair was elucidated by RNA immunoprecipitation and luciferase reporter assays. Finally, the corrections between Hotair, miR-218 and the target gene @entity3752 were evaluated in 52 paired @entity157 specimens. RESULTS: In this study, we reported that Hotair negatively regulated miR-218 expression in @entity157 , which might be mediated through an EZH2-targeting-miR-218-2 promoter regulatory axis. Further investigation revealed that Hotair knockdown dramatically inhibited cell viability and induced G1-phase arrest in vitro and suppressed tumorigenicity in vivo by promoting miR-218 expression. Oncogene @entity3752 was demonstrated to be a functional target of miR-218 and the main downstream targets @entity986 ( @entity986 ) and @entity986 (ARF) signaling were activated in Hotair-suppressed tumorigenesis. In primary @entity1 @entity157 specimens, Hotair and @entity3752 were concordantly upregulated whereas miR-218 was downregulated in these tissues. Furthermore, Hotair was inversely associated with miR-218 expression and positively correlated with @entity3752 expression in these clinical tissues. CONCLUSION: Hotair silence activates @entity986 ( @entity986 ) and @entity986 (ARF) signaling by enhancing miR-218 expression and suppressing @entity3752 expression, resulting in the suppression of tumorigenesis in @entity157 .
