The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
LncRNA HOTAIR Enhances the Androgen-Receptor-Mediated Transcriptional Program and Drives Castration-Resistant Prostate Cancer
Open accessAbstract
Understanding the mechanisms of androgen receptor (AR) activation in the milieu of low androgen is critical to effective treatment of castration-resistant prostate cancer (CRPC). Here, we report HOTAIR as an androgen-repressed lncRNA, and, as such, it is markedly upregulated following androgen deprivation therapies and in CRPC. We further demonstrate a distinct mode of lncRNA-mediated gene regulation, wherein HOTAIR binds to the AR protein to block its interaction with the E3 ubiquitin ligase MDM2, thereby preventing AR ubiquitination and protein degradation. Consequently, HOTAIR expression is sufficient to induce androgen-independent AR activation and drive the AR-mediated transcriptional program in the absence of androgen. Functionally, HOTAIR overexpression increases, whereas HOTAIR knockdown decreases, prostate cancer cell growth and invasion. Taken together, our results provide compelling evidence of lncRNAs as drivers of androgen-independent AR activity and CRPC progression, and they support the potential of lncRNAs as therapeutic targets.
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“The lncRNA HOTAIR has been shown to bind PRC2 through its 5′ region but to bind the LSD1/REST complex with its 3′ domain, thereby serving as scaffolds that coordinate co-targeting of these proteins to selected chromatin regions (Tsai et al., 2010).”
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Cited by
Zhou, C., Yi, C., Yi, Y., Qin, W., Yan, Y., Dong, X., Zhang, X., Huang, Y., Zhang, R., Wei, J., et al. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01237-y · Cited by 382
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Metadata
- Authors
- Zhang, A., Zhao, J. C., Kim, J., Fong, K.-W., Yang, Y. A., Chakravarti, D., Mo, Y.-Y., & Yu, J.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 13
- Issue
- 1
- Pages
- 209-221
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2122175755
- Cited by
- 339
- References
- 31
- FWCI
- 19.98
- Type
- journal article
- Language
- en
- Open access
- gold
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- Zhang, A., Zhao, J. C., Kim, J., Fong, K.-W., Yang, Y. A., Chakravarti, D., Mo, Y.-Y., & Yu, J. (2015). LncRNA HOTAIR Enhances the Androgen-Receptor-Mediated Transcriptional Program and Drives Castration-Resistant Prostate Cancer. Cell Reports. https://doi.org/10.1016/j.celrep.2015.08.069
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