NOVEL LONG NON-CODING RNA MIR205HG: AN ESOPHAGEAL TUMOR-SUPPRESSIVE HEDGEHOG INHIBITOR
Song, Jee Hoon
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Esophageal adenocarcinoma (EAC) is one of the most rapidly increasing cancers in Western countries, but its underlying molecular mechanisms have not yet been fully elucidated. Recently, the discovery of long non-coding RNAs (lncRNAs) has added a new layer of complexity to the molecular architecture, identifying these molecules as emerging key regulators of diverse biological pathways. Increasing evidence shows that lncRNA dysregulation can lead to many diseases, including cancer, but their potential involvement in EAC is not yet well-understood. In this study, we used massively parallel RNA sequencing to identify a set of lncRNAs that were differentially expressed in esophageal cancers vs. normal esophageal epithelia. After a rigorous filtering procedure, miR205HG was found to be strikingly downregulated in EAC cell lines and tissues. In vitro assays in EAC cell lines demonstrated that overexpression of miR205HG inhibited cell proliferation, cell cycle progression, and colony formation. Moreover, in vivo mouse xenograft experiments using miR205HG-stably transfected EAC cells revealed that forced miR205HG overexpression inhibited tumor growth in nude mice. We then posited that miR205HG’s mechanism of action involved the Hedgehog (HH) signaling pathway, since miR205HG and SHH expression levels were found to inversely correlate in patient EAC (r= -0.73) and BE (r= -0.83) tissues. Furthermore, miR205HG overexpression was shown to inhibit sonic hedgehog (SHH) transcription and translation. In summary, our findings suggested that miR205HG is involved in the development and/or progression of EAC and offers potential as a therapeutic target and a prognostic biomarker.