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Long noncoding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many types of human cancers. The lncRNA  ANRIL  is transcribed from the  INK4b‐ARF‐INK4a  gene cluster in the opposite direction. Whether  ANRIL  can act as an oncogenic molecule in cholangiocarcinoma (CCA) remains unknown. Our data show that  ANRIL  knockdown greatly inhibited CCA cell proliferation and migration in vitro and in vivo. According to the results of RNA sequencing analysis,  ANRIL  knockdown dramatically altered target genes associated with the cell cycle, cell proliferation, and apoptosis. By binding to a component of the epigenetic modification complex enhancer of zeste homolog 2 (EZH2),  ANRIL  could maintain lysine residue 27 of histone 3 (H3K27me3) levels in the promoter of ERBB receptor feedback inhibitor 1 ( ERRFI1 ), which is a tumor suppressor gene in CCA. In this way,  ERRFI1  expression was suppressed in CCA cells. These data verified the key role of the epigenetic regulation of  ANRIL  in CCA oncogenesis and indicate its potential as a target for CCA intervention.

Long noncoding RNA ANRIL promotes the malignant progression of cholangiocarcinoma by epigenetically repressing ERRFI1 expression