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长链非编码RNA H19在食管鳞状细胞癌中上调,并促进细胞增殖和转移。

Long noncoding RNA H19 is up-regulated in esophageal squamous cell carcinoma and promotes cell proliferation and metastasis.

作者信息

Tan Deli, Wu Yuanyuan, Hu Liwen, He Ping, Xiong Gang, Bai Yun, Yang Kang

机构信息

Department of Cardiothoracic Surgery, Southwest Hospital, Chongqing, China.

Department of Medical Genetics, College of Basic Medical Science, Third Military Medical University, Chongqing, China.

出版信息

Dis Esophagus. 2017 Jan 1;30(1):1-9. doi: 10.1111/dote.12481.

Abstract

Long noncoding RNAs (lncRNAs) have been shown to play various roles in tumorigenesis, among which lncRNA H19 has been revealed as an ambivalent factor that acts as both an oncogene and a tumor suppressor in carcinogenesis. However, the exact biological role of H19 in esophageal squamous cell carcinoma (ESCC) remains to be determined. The aim of this study was to examine the expression pattern of H19 in ESCC and evaluate its biological role and clinical significance in the progression of ESCC. Expression of H19 was analyzed in 64 ESCC tissues and four ESCC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Proliferation, cell cycle, migration, and invasion assays were performed in ESCC cell lines following knockdown of H19 to determine the biological function of H19 in the progression of ESCC both in vitro and in vivo. Western blot analysis was also performed to identify the potential mechanisms involved. H19 was highly expressed both in ESCC samples and cell lines compared with corresponding normal counterparts. The up-regulation of of H19 was significantly correlated with ESCC clinical stage and lymph node metastasis. Knockdown of H19 not only exerted inhibitory effect on tumor proliferation in vitro and in vivo, but also repressed the migratory and invasive capacity. G0/G1 phase arrest was also found in H19 knockdown cell lines. In addition, silencing of H19 up-regulated epithelial marker E-cadherin while down-regulating mesenchymal marker vimentin and metastasis-associated protein such as MMP-9. These findings indicate that H19 acts as an oncogene and promotes ESCC cell proliferation and metastasis, which may infer H19 as a marker of poor prognosis and, thus, a potential therapeutic target for treating ESCC patients.

摘要

长链非编码RNA(lncRNAs)已被证明在肿瘤发生中发挥多种作用,其中lncRNA H19已被揭示为一种矛盾的因子,在致癌过程中既作为癌基因又作为肿瘤抑制因子。然而,H19在食管鳞状细胞癌(ESCC)中的确切生物学作用仍有待确定。本研究的目的是检测H19在ESCC中的表达模式,并评估其在ESCC进展中的生物学作用和临床意义。通过定量逆转录聚合酶链反应(qRT-PCR)分析了64例ESCC组织和4种ESCC细胞系中H19的表达。在敲低H19后的ESCC细胞系中进行增殖、细胞周期、迁移和侵袭实验,以确定H19在ESCC体外和体内进展中的生物学功能。还进行了蛋白质免疫印迹分析以确定潜在的相关机制。与相应的正常对照相比,H19在ESCC样本和细胞系中均高表达。H19的上调与ESCC临床分期和淋巴结转移显著相关。敲低H19不仅在体外和体内对肿瘤增殖产生抑制作用,还抑制了迁移和侵袭能力。在敲低H19的细胞系中也发现了G0/G1期阻滞。此外,沉默H19可上调上皮标志物E-钙黏蛋白,同时下调间充质标志物波形蛋白和转移相关蛋白如MMP-9。这些发现表明,H19作为一种癌基因促进ESCC细胞增殖和转移,这可能意味着H19是预后不良的标志物,因此是治疗ESCC患者的潜在治疗靶点。

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