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Article

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

1
Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
2
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21287, USA
3
Division of Gastroenterology and Hepatology, Department of Medicine, Eastern Virginia Medical School, Norfolk, VA 23456, USA
*
Author to whom correspondence should be addressed.
The first two authors contributed equally to this article.
Academic Editors: Gabriella Misso, Angela Lombardi, Agostino Festa and Mary Frances McMullin
Cancers 2021, 13(7), 1707; https://doi.org/10.3390/cancers13071707
Received: 16 March 2021 / Accepted: 24 March 2021 / Published: 3 April 2021
Barrett’s esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Long noncoding RNAs (lncRNAs) have been identified as key regulators of biological pathways and we identified lncRNA, miR205HG, as a tumor suppressor in the development of Barrett’s esophagus and esophageal adenocarcinoma, in part through its effect on the Hedgehog signaling pathway. The aims of the current study were: (1) to study involvement of miR205HG in the development of BE and EAC (2) to clarify the role of miR205HG in in vitro and in vivo experiments; and (3) to investigate the mechanism of miR205HG involving the Hedgehog (Hh) signaling pathway
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, miR205HG, in the development of BE and EAC; (2) to clarify the role of miR205HG in in vitro and in vivo experiments; and (3) to investigate the mechanism of miR205HG involving the Hedgehog (Hh) signaling pathway. These experiments revealed that miR205HG 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 miR205HG inhibited xenograft tumor growth in mice In vivo. Finally, we show that one mechanism of action of miR205HG involves the Hh signaling pathway: miR205HG 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 miR205HG. In conclusion, these findings establish that lncRNA miR205HG functions as a tumor suppressor in the development of BE and EAC, at least in part through its effect on the Hh signaling pathway. View Full-Text
Keywords: esophageal adenocarcinoma (EAC); Barrett’s esophagus; long noncoding RNA (lncRNAs); hedgehog inhibitor esophageal adenocarcinoma (EAC); Barrett’s esophagus; long noncoding RNA (lncRNAs); hedgehog inhibitor
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MDPI and ACS Style

Song, J.H.; Tieu, A.H.; Cheng, Y.; Ma, K.; Akshintala, V.S.; Simsek, C.; Prasath, V.; Shin, E.J.; Ngamruengphong, S.; Khashab, M.A.; Abraham, J.M.; Meltzer, S.J. Novel Long Noncoding RNA miR205HG Functions as an Esophageal Tumor-Suppressive Hedgehog Inhibitor. Cancers 2021, 13, 1707. https://doi.org/10.3390/cancers13071707

AMA Style

Song JH, Tieu AH, Cheng Y, Ma K, Akshintala VS, Simsek C, Prasath V, Shin EJ, Ngamruengphong S, Khashab MA, Abraham JM, Meltzer SJ. Novel Long Noncoding RNA miR205HG Functions as an Esophageal Tumor-Suppressive Hedgehog Inhibitor. Cancers. 2021; 13(7):1707. https://doi.org/10.3390/cancers13071707

Chicago/Turabian Style

Song, Jee H., Alan H. Tieu, Yulan Cheng, Ke Ma, Venkata S. Akshintala, Cem Simsek, Vishnu Prasath, Eun J. Shin, Saowanee Ngamruengphong, Mouen A. Khashab, John M. Abraham, and Stephen J. Meltzer. 2021. "Novel Long Noncoding RNA miR205HG Functions as an Esophageal Tumor-Suppressive Hedgehog Inhibitor" Cancers 13, no. 7: 1707. https://doi.org/10.3390/cancers13071707

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