Song Jee Hoon, Tieu Alan H, Cheng Yulan, Ma Ke, Akshintala Venkata S, Simsek Cem, Prasath Vishnu, Shin Eun Ji, Ngamruengphong Saowanee, Khashab Mouen A, Abraham John M, Meltzer Stephen J
Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21287, USA.
Cancers (Basel). 2021 Apr 3;13(7):1707. doi: 10.3390/cancers13071707.
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, , in the development of BE and EAC; (2) to clarify the role of in in vitro and in vivo experiments; and (3) to investigate the mechanism of involving the Hedgehog (Hh) signaling pathway. These experiments revealed that 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 inhibited xenograft tumor growth in mice In vivo. Finally, we show that one mechanism of action of involves the Hh signaling pathway: 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 In conclusion, these findings establish that lncRNA functions as a tumor suppressor in the development of BE and EAC, at least in part through its effect on the Hh signaling pathway.
巴雷特食管（BE）是食管腺癌（EAC）的癌前病变。最近，长链非编码RNA（lncRNAs）已被确定为生物途径的关键调节因子。然而，lncRNAs在BE和EAC发生发展中的作用尚未得到充分研究。本研究的目的是：（1）研究lncRNA在BE和EAC发生发展中的作用；（2）在体外和体内实验中阐明其作用；（3）研究其涉及刺猬（Hh）信号通路的机制。这些实验表明，与正常食管上皮（NE）以及EAC细胞系相比，EAC中该lncRNA表达下调，其强制过表达在体外抑制EAC细胞增殖和细胞周期进程。同样，在体内过表达该lncRNA可抑制小鼠异种移植瘤的生长。最后，我们表明该lncRNA的一种作用机制涉及Hh信号通路：在EAC组织（r = -0.73）和BE组织（r = -0.83）中，该lncRNA与Hh表达水平呈负相关，体外研究揭示了该lncRNA诱导Hh信号抑制的详细情况。总之，这些发现表明lncRNA在BE和EAC的发生发展中起肿瘤抑制作用，至少部分是通过其对Hh信号通路的影响。
