Long non-coding RNA-Low Expression in Tumor inhibits the invasion and metastasis of esophageal squamous cell carcinoma by regulating p53 expression.

Long non-coding RNA-Low Expression in Tumor inhibits the invasion and metastasis of esophageal squamous cell carcinoma by regulating p53 expression.
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DOI:
10.3892/mmr.2016.4913
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发表时间:
2016-04
影响因子:
3.4
通讯作者:
Chen YJ
Chen YJ
中科院分区:
医学4区
文献类型:
--
作者:
Wang PL;Liu B;Xia Y;Pan CF;Ma T;Chen YJ

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长非编码RNA(Long Non-Coding RNAs,LncRNAs)参与调控基本的生物学过程,在许多LncRNAs中,其表达水平发生改变,可能在肿瘤的发生中发挥作用,包括细胞凋亡、迁移和侵袭。肿瘤低表达(LET)是新近发现的一种新发现的LncRNA,在肝细胞癌和胆囊癌中表达下调。然而,它在食管鳞癌(ESCC)中的作用还有待研究。采用逆转录-定量聚合酶链式反应方法检测48例原发ESCC及其配对的正常组织中LncRNA-let的表达水平。此外,用流式细胞仪检测lncRNA-let对细胞凋亡的影响,用伤口愈合实验检测lncRNA-let对细胞迁移的调节作用,用Matrigel包被的Transwell实验检测细胞侵袭能力。用5-乙炔基-2‘-脱氧尿嘧啶核苷细胞增殖实验检测lncRNA-let对细胞增殖的影响,并用Western blotting分析靶蛋白的蛋白水平。与配对的健康组织相比,原发ESCC组织中LncRNA-let的表达降低,并被证实与临床特征有关。在体外,我们观察到LncRNA-let的过表达可以抑制人ESCC细胞的迁移和侵袭,并调节P53的表达水平。这些结果表明,lncRNA-let在肿瘤的进展和转移中具有重要的调控作用,并且在人ESCC的治疗中作为一种肿瘤抑制因子,因此具有治疗潜力。
Long non-coding RNAs (lncRNAs) are involved in governing fundamental biological processes, and, in many lncRNAs, the expression level is altered and likely to have a functional role in tumorigenesis, including apoptosis, migration and invasion. The lncRNA-Low Expression in Tumor (LET), a recently identified lncRNA, was demonstrated to be downregulated in hepatocellular and gallbladder cancer. However, its role in esophageal squamous cell carcinoma (ESCC) requires investigation. The expression level of lncRNA-LET mRNA in primary ESCC and matched healthy tissues (48 cases) was determined by reverse transcription-quantitative polymerase chain reaction. In addition, the effects of lncRNA-LET on cell apoptosis were evaluated by flow cytometric analysis, the regulatory effect of lncRNA-LET on migration was detected using a wound healing assay and cellular invasion was analyzed by Matrigel-coated transwell assay. Furthermore, the effect of lncRNA-LET on cell proliferation was investigated by 5-ethynyl-2′-deoxyuridine cell proliferation assay and protein levels of lncRNA-LET targets were analyzed by western blotting. lncRNA-LET expression was decreased in primary ESCC tissues when compared with paired healthy tissues, and was identified to be associated with the clinical features. Overexpression of lncRNA-LET was observed to inhibit the migration and invasion of ESCC cells, and modulate p53 expression levels in human ESCC cell lines in vitro. These results establish that lncRNA-LET is significant in the regulation of tumor progression and metastasis, and serves as a tumor suppressor in, and therefore has therapeutic potential for, the treatment of human ESCC.