Upregulation of miR-196a and HOTAIR Drive Malignant Character in Gastrointestinal Stromal Tumors
2012; American Association for Cancer Research; Volume: 72; Issue: 5 Linguagem: Inglês
10.1158/0008-5472.can-11-1803
ISSN1538-7445
AutoresTakeshi Niinuma, Hiromu Suzuki, Masanori Nojima, Katsuhiko Nosho, Hiroyuki Yamamoto, Hiroyuki Takamaru, Eiichiro Yamamoto, Reo Maruyama, Takayuki Nobuoka, Yasuaki Miyazaki, Toshirou Nishida, Takeo Bamba, Tatsuo Kanda, Yoichi Ajioka, Takahiro Taguchi, Satoshi Okahara, Hiroaki Takahashi, Yasunori Nishida, Masao Hosokawa, Tadashi Hasegawa, Takashi Tokino, Koichi Hirata, Kohzoh Imai, Minoru Toyota, Yasuhisa Shinomura,
Tópico(s)Tumors and Oncological Cases
ResumoAbstract 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 HOXC and 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. ©2012 AACR.
Referência(s)