Enhanced Expression of Long Non-Coding RNA HOTAIR Is Associated with the Development of Gastric Cancer

被引：238

作者：

Endo, Hiroyuki ^{[1
,5
]}

Shiroki, Takeharu ^{[1
,5
]}

Nakagawa, Takayuki ^{[1
]}

Yokoyama, Misa ^{[1
]}

Tamai, Keiichi ^{[2
]}

Yamanami, Hideaki ^{[3
]}

Fujiya, Tsuneaki ^{[3
]}

Sato, Ikuro ^{[4
]}

Yamaguchi, Kazunori ^{[2
]}

Tanaka, Nobuyuki ^{[2
]}

Iijima, Katsunori ^{[5
]}

Shimosegawa, Tooru ^{[5
]}

Sugamura, Kazuo ^{[2
]}

Satoh, Kennichi ^{[1
]}

机构：

[1] Miyagi Canc Ctr, Res Inst, Div Canc Stem Cell, Natori, Miyagi 9811293, Japan

[2] Miyagi Canc Ctr, Res Inst, Natori, Miyagi 9811293, Japan

[3] Miyagi Canc Ctr, Dept Surg, Natori, Miyagi 9811293, Japan

[4] Miyagi Canc Ctr, Dept Pathol, Natori, Miyagi 9811293, Japan

[5] Tohoku Univ, Div Gastroenterol, Grad Sch Med, Sendai, Miyagi 980, Japan

来源：

PLOS ONE | 2013年 / 8卷 / 10期

关键词：

CARCINOMA PROGRESSION; SURVIVAL; ELEMENTS; PROJECT;

D O I：

10.1371/journal.pone.0077070

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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