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.
Highlights
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract [1,2,3]
The results of recent studies suggest that the gene expression signatures of GISTs are predictive of malignancy and drug sensitivity of the tumors [5, 21], the clinical significance of the miRNA expression signature is not yet fully understood
We found that upregulation of miR-196a is strongly associated with a high-risk grade, metastasis, and poor prognosis in GIST patients
Summary
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract [1,2,3].
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