Upregulation of miR-196a and HOTAIR Drive Malignant Character in Gastrointestinal Stromal Tumors

被引：321

作者：

Niinuma, Takeshi ^{[2
]}

Suzuki, Hiromu ^{[1
,2
]}

Nojima, Masanori ^{[4
]}

Nosho, Katsuhiko ^{[2
]}

Yamamoto, Hiroyuki ^{[2
]}

Takamaru, Hiroyuki ^{[2
]}

Yamamoto, Eiichiro ^{[1
]}

Maruyama, Reo ^{[1
]}

Nobuoka, Takayuki ^{[3
]}

Miyazaki, Yasuaki ^{[9
]}

Nishida, Toshirou ^{[9
,10
]}

Bamba, Takeo ^{[11
]}

Kanda, Tatsuo

Ajioka, Yoichi ^{[12
]}

Taguchi, Takahiro ^{[13
]}

Okahara, Satoshi ^{[7
]}

Takahashi, Hiroaki ^{[7
]}

Nishida, Yasunori ^{[8
]}

Hosokawa, Masao ^{[8
]}

Hasegawa, Tadashi ^{[5
]}

Tokino, Takashi ^{[6
]}

Hirata, Koichi ^{[3
]}

Imai, Kohzoh ^{[14
]}

Toyota, Minoru ^{[1
]}

Shinomura, Yasuhisa ^{[2
]}

机构：

[1] Sapporo Med Univ, Sch Med, Res Inst Frontier Med, Dept Mol Biol,Chuo Ku, Sapporo, Hokkaido 0608556, Japan

[2] Sapporo Med Univ, Sch Med, Res Inst Frontier Med, Dept Internal Med, Sapporo, Hokkaido 0608556, Japan

[3] Sapporo Med Univ, Sch Med, Res Inst Frontier Med, Dept Surg, Sapporo, Hokkaido 0608556, Japan

[4] Sapporo Med Univ, Sch Med, Res Inst Frontier Med, Dept Publ Hlth, Sapporo, Hokkaido 0608556, Japan

[5] Sapporo Med Univ, Sch Med, Res Inst Frontier Med, Dept Surg Pathol, Sapporo, Hokkaido 0608556, Japan

[6] Sapporo Med Univ, Sch Med, Res Inst Frontier Med, Dept Med Genome Sci, Sapporo, Hokkaido 0608556, Japan

[7] Keiyukai Sapporo Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan

[8] Keiyukai Sapporo Hosp, Dept Surg, Sapporo, Hokkaido, Japan

[9] Osaka Univ, Grad Sch Med, Dept Surg, Osaka, Japan

[10] Osaka Police Hosp, Dept Surg, Osaka, Japan

[11] Niigata Univ, Grad Sch Med & Dent Sci, Div Digest & Gen Surg, Niigata, Japan

[12] Niigata Univ, Grad Sch Med & Dent Sci, Div Mol & Diagnost Pathol, Niigata, Japan

[13] Kochi Univ, Grad Sch Kuroshio Sci, Div Human Hlth & Med Sci, Nankoku, Kochi, Japan

[14] Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Novel Theraphy Canc, Tokyo, Japan

来源：

CANCER RESEARCH | 2012年 / 72卷 / 05期

关键词：

LONG NONCODING RNA; MICRORNA EXPRESSION; HUMAN PROSTATE; MESSENGER-RNA; CANCER; SIGNATURES; GENES; HOXC8; OVEREXPRESSION; ADENOCARCINOMA;

D O I：

10.1158/0008-5472.CAN-11-1803

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Large intergenic noncoding RNAs (lincRNA) have been less studied than miRNAs in cancer, although both offer considerable theranostic potential. In this study, we identified frequent upregulation of miR-196a and lincRNA HOTAIR in high-risk gastrointestinal stromal tumors (GIST). Overexpression of miR-196a was associated with high-risk grade, metastasis and poor survival among GIST specimens. miR-196a genes are located within the HOX gene clusters and microarray expression analysis revealed that the HOXCand HOTAIR gene were also coordinately upregulated in GISTs which overexpress miR-196a. In like manner, overexpression of HOTAIR was also strongly associated with high-risk grade and metastasis among GIST specimens. RNA interference-mediated knockdown of HOTAIR altered the expression of reported HOTAIR target genes and suppressed GIST cell invasiveness. These findings reveal concurrent overexpression of HOX genes with noncoding RNAs in human cancer in this setting, revealing miR-196a and HOTAIR as potentially useful biomarkers and therapeutic targets in malignant GISTs. Cancer Res; 72(5); 1126-36. (C) 2012 AACR.

引用

页码：1126 / 1136

页数：11

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