Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer.

Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer.
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DOI:
10.1371/journal.pone.0077070
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Satoh K
Satoh K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Endo H;Shiroki T;Nakagawa T;Yokoyama M;Tamai K;Yamanami H;Fujiya T;Sato I;Yamaguchi K;Tanaka N;Iijima K;Shimosegawa T;Sugamura K;Satoh K

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据报道,长链非编码RNA HOTAIR是多种恶性肿瘤预后不良的生物标志物。然而,人们对HOTAIR与胃癌的关系知之甚少。我们采用实时荧光定量RT-PCR检测了68例胃癌标本中HOTAIR的表达,并分析其与临床参数的相关性。通过培养HOTAIR表达升高或抑制的人胃癌细胞株,研究了HOTAIR的功能作用。采用软琼脂法测定非锚定生长。将增加或抑制HOTAIR表达的胃癌细胞注射到免疫缺陷小鼠的尾静脉或腹膜腔,观察该分子对转移和腹膜播散的影响。HOTAIR在人胃癌癌灶中的表达明显高于癌旁非癌组织。在弥漫性胃癌中,与低HOTAIR组(HOTAIR/GAPDH < 1)相比,高HOTAIR组(HOTAIR/GAPDH > 1)明显表现出更多的静脉侵犯、频繁的淋巴结转移和更低的总生存率。软琼脂上的菌落形成以hotair依赖性的方式增强。当将表达hotair的MKN74注射到小鼠的尾静脉中时,与对照组相比,它们形成了更多的肝转移。此外,KATO III中HOTAIR表达的降低抑制了腹膜传播。这些结果提示HOTAIR在胃癌的发生发展中起着关键作用。
The long non-coding RNA HOTAIR has been reported to be a poor prognostic biomarker in a variety of malignant tumors. However, little is known about the association of HOTAIR with gastric cancer. We examined the expression of HOTAIR in 68 gastric cancer samples using quantitative real-time RT-PCR and analyzed its correlation with the clinical parameters. The functional role of HOTAIR was examined by generating human gastric cancer cell lines with increased or suppressed HOTAIR expression. The anchorage -independent growth was assessed by soft agar assay. The increased or suppressed HOTAIR expressing gastric cancer cells were injected into the tail vein or peritoneal cavity of immunodeficient mice to examine the effect of this molecule on metastasis and peritoneal dissemination. The expression of HOTAIR was significantly higher in cancer lesions than in adjacent non-cancerous tissues in human gastric cancers. In the diffuse type of gastric cancer, the High-HOTAIR group (HOTAIR/GAPDH > 1) showed significantly more venous invasion, frequent lymph node metastases and a lower overall survival rate compared to the Low-HOTAIR group (HOTAIR/GAPDH < 1). Colony formation on the soft agar was enhanced in a HOTAIR-dependent manner. HOTAIR-expressing MKN74 formed more liver metastasis compared to control when they were injected into the tail vein of mice. In addition, reduced expression of HOTAIR in KATO III suppressed peritoneal dissemination. These results suggest that HOTAIR plays a pivotal role in the development of gastric cancer.
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