Novel Long Noncoding RNA miR205HG Functions as an Esophageal Tumor-Suppressive Hedgehog Inhibitor

Abstract

Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators of biological pathways. However, involvement of lncRNAs in the development of BE and EAC has not been well-studied. The aims of the current study were: (1) to study involvement of the lncRNA, <i>miR205HG</i>, in the development of BE and EAC; (2) to clarify the role of <i>miR205HG</i> in in vitro and in vivo experiments; and (3) to investigate the mechanism of <i>miR205HG</i> involving the Hedgehog (Hh) signaling pathway. These experiments revealed that <i>miR205HG</i> was downregulated in EAC vs. normal esophageal epithelia (NE) as well as in EAC cell lines, and its forced overexpression inhibited EAC cell proliferation and cell cycle progression in vitro. Similarly, overexpression of <i>miR205HG</i> inhibited xenograft tumor growth in mice In vivo. Finally, we show that one mechanism of action of <i>miR205HG</i> involves the Hh signaling pathway: <i>miR205HG</i> and Hh expression levels were inversely correlated in both EAC (r = -0.73) and BE (r = -0.83) tissues, and in vitro studies revealed details of Hh signaling inhibition induced by <i>miR205HG.</i> In conclusion, these findings establish that lncRNA <i>miR205HG</i> functions as a tumor suppressor in the development of BE and EAC, at least in part through its effect on the Hh signaling pathway.