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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. Cancer Res; 72(5); 1126–36. ©2012 AACR.
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Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes
Tsai, M.-C., Manor, O., Wan, Y., Mosammaparast, N., Wang, J. K., Lan, F., Shi, Y., Segal, E., & Chang, H. Y. (2010) · Science · doi:10.1126/science.1192002 · Cited by 3,290
Epigenetic Regulation of Cell Type–Specific Expression Patterns in the Human Mammary Epithelium
Maruyama, R., Choudhury, S., Kowalczyk, A., Bessarabova, M., Beresford-Smith, B., Conway, T., Kaspi, A., Wu, Z., Nikolskaya, T., Merino, V. F., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001369 · Cited by 108
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Kung, J. T. Y., Colognori, D., & Lee, J. T. (2013) · Genetics · doi:10.1534/genetics.112.146704 · Cited by 1,874
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Yang, G., Lu, X., & Yuan, L. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.08.012 · Cited by 991
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Chen, X., Yan, C. C., Zhang, X., & You, Z.-H. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw060 · Cited by 567
Targeting long non-coding RNA to therapeutically upregulate gene expression
Wahlestedt, C. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4018 · Cited by 532
Metadata
- Authors
- Niinuma, T., Suzuki, H., Nojima, M., Nosho, K., Yamamoto, H., Takamaru, H., Yamamoto, E., Maruyama, R., Nobuoka, T., Miyazaki, Y., Nishida, T., Bamba, T., Kanda, T., Ajioka, Y., Taguchi, T., Okahara, S., Takahashi, H., Nishida, Y., Hosokawa, M., Hasegawa, T., Tokino, T., Hirata, K., Imai, K., Toyota, M., & Shinomura, Y.
- Venue
- Cancer Research
- Published
- 2012-03-01
- Volume
- 72
- Issue
- 5
- Pages
- 1126-1136
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2166652958
- Cited by
- 354
- References
- 2
- FWCI
- 14.33
- Type
- journal article
- Language
- en
- Open access
- closed
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- Niinuma, T., Suzuki, H., Nojima, M., Nosho, K., Yamamoto, H., Takamaru, H., Yamamoto, E., Maruyama, R., Nobuoka, T., Miyazaki, Y., Nishida, T., Bamba, T., Kanda, T., Ajioka, Y., Taguchi, T., Okahara, S., Takahashi, H., Nishida, Y., Hosokawa, M., . . . Shinomura, Y. (2012). Upregulation of miR-196a and HOTAIR Drive Malignant Character in Gastrointestinal Stromal Tumors. Cancer Research. https://doi.org/10.1158/0008-5472.can-11-1803
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