Li Jie, Han Xu, Gu Yan, Wu Jixiang, Song Jianxiang, Shi Zhan, Chang Huiwen, Liu Ming, Zhang Yajun
The First School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
Department of Cardiothoracic Surgery, Yancheng Third People's Hospital, The Sixth Affiliated Hospital of Nantong University, Yancheng, China.
Front Cell Dev Biol. 2021 Mar 23;9:654746. doi: 10.3389/fcell.2021.654746. eCollection 2021.
Esophageal squamous cell carcinoma (ESCC) has been one of the key causes of cancer deaths worldwide. It has been found that long non-coding RNA (lncRNA) is related to the generation and progression of various cancers (including ESCC). However, there are still many lncRNAs related to ESCC whose functions and molecular mechanisms have not been clearly elucidated. In this study, we first reported that lncRNA MTX2-6 was significantly downregulated in ESCC tissues and cell lines. The decreased expression of MTX2-6 is closely related to larger tumor and worse prognosis of ESCC patients. Through a series of functional experiments, we detected that overexpressed MTX2-6 inhibited cell proliferation and promoted cell apoptosis of ESCC and . Further studies showed that MTX2-6 exerts as a competing endogenous RNA (ceRNA) by binding miR-574-5p and elevates the expression of SMAD4 in ESCC. In summary, our results clarify the tumor suppressor roles of MTX2-6/miR-574-5p/SMAD4 axis in the progression of ESCC and provide emerging therapeutic targets for ESCC patients.
食管鳞状细胞癌（ESCC）一直是全球癌症死亡的主要原因之一。研究发现，长链非编码RNA（lncRNA）与包括ESCC在内的多种癌症的发生和发展有关。然而，仍有许多与ESCC相关的lncRNA，其功能和分子机制尚未明确阐明。在本研究中，我们首次报道lncRNA MTX2-6在ESCC组织和细胞系中显著下调。MTX2-6表达降低与ESCC患者的肿瘤较大及预后较差密切相关。通过一系列功能实验，我们检测到过表达MTX2-6可抑制ESCC细胞增殖并促进其凋亡。进一步研究表明，MTX2-6作为竞争性内源RNA（ceRNA）通过结合miR-574-5p来提高ESCC中SMAD4的表达。总之，我们的结果阐明了MTX2-6/miR-574-5p/SMAD4轴在ESCC进展中的肿瘤抑制作用，并为ESCC患者提供了新的治疗靶点。
