title: Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Niinuma
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Masanori
authors.initials: M
authors.lastname: Nojima
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nosho
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamaru
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Reo
authors.initials: R
authors.lastname: Maruyama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nobuoka
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
authors.forename: Takeo
authors.initials: T
authors.lastname: Bamba
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okahara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Nishida
authors.forename: Masao
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokino
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyota
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C561566:HOTAIR long untranslated RNA, human; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated