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LINC00675 activates androgen receptor axis signaling pathway to promote castration-resistant prostate cancer progression.

Publication ,  Journal Article
Yao, M; Shi, X; Li, Y; Xiao, Y; Butler, W; Huang, Y; Du, L; Wu, T; Bian, X; Shi, G; Ye, D; Fu, G; Wang, J; Ren, S
Published in: Cell death & disease
August 2020

The development of prostate cancer (PCa) from androgen-deprivation therapy (ADT) sensitive to castration resistant (CRPC) seriously impacts life quality and survival of PCa patients. Emerging evidence shows that long noncoding RNAs (lncRNAs) play vital roles in cancer initiation and progression. However, the inherited mechanisms of how lncRNAs participate in PCa progression and treatment resistance remain unclear. Here, we found that a long noncoding RNA LINC00675 was upregulated in androgen-insensitive PCa cell lines and CRPC patients, which promoted PCa progression both in vitro and in vivo. Knockdown of LINC00675 markedly suppressed tumor formation and attenuated enzalutamide resistance of PCa cells. Mechanistically, LINC00675 could directly modulate androgen receptor's (AR) interaction with mouse double minute-2 (MDM2) and block AR's ubiquitination by binding to it. Meanwhile, LINC00675 could bind to GATA2 mRNA and stabilize its expression level, in which GATA2 could act as a co-activator in the AR signaling pathway. Notably, we treated subcutaneous xenografts models with enzalutamide and antisense oligonucleotides (ASO) targeting LINC00675 in vivo and found that targeting LINC00675 would benefit androgen-deprivation-insensitive models. Our findings disclose that the LINC00675/MDM2/GATA2/AR signaling axis is a potential therapeutic target for CRPC patients.

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Published In

Cell death & disease

DOI

EISSN

2041-4889

ISSN

2041-4889

Publication Date

August 2020

Volume

11

Issue

8

Start / End Page

638

Related Subject Headings

  • Signal Transduction
  • Receptors, Androgen
  • RNA, Long Noncoding
  • Prostatic Neoplasms, Castration-Resistant
  • Prostatic Neoplasms
  • Phenylthiohydantoin
  • Nitriles
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
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Yao, M., Shi, X., Li, Y., Xiao, Y., Butler, W., Huang, Y., … Ren, S. (2020). LINC00675 activates androgen receptor axis signaling pathway to promote castration-resistant prostate cancer progression. Cell Death & Disease, 11(8), 638. https://doi.org/10.1038/s41419-020-02856-5
Yao, Mengfei, Xiaolei Shi, Yue Li, Yutian Xiao, William Butler, Yongqiang Huang, Leilei Du, et al. “LINC00675 activates androgen receptor axis signaling pathway to promote castration-resistant prostate cancer progression.Cell Death & Disease 11, no. 8 (August 2020): 638. https://doi.org/10.1038/s41419-020-02856-5.
Yao M, Shi X, Li Y, Xiao Y, Butler W, Huang Y, et al. LINC00675 activates androgen receptor axis signaling pathway to promote castration-resistant prostate cancer progression. Cell death & disease. 2020 Aug;11(8):638.
Yao, Mengfei, et al. “LINC00675 activates androgen receptor axis signaling pathway to promote castration-resistant prostate cancer progression.Cell Death & Disease, vol. 11, no. 8, Aug. 2020, p. 638. Epmc, doi:10.1038/s41419-020-02856-5.
Yao M, Shi X, Li Y, Xiao Y, Butler W, Huang Y, Du L, Wu T, Bian X, Shi G, Ye D, Fu G, Wang J, Ren S. LINC00675 activates androgen receptor axis signaling pathway to promote castration-resistant prostate cancer progression. Cell death & disease. 2020 Aug;11(8):638.

Published In

Cell death & disease

DOI

EISSN

2041-4889

ISSN

2041-4889

Publication Date

August 2020

Volume

11

Issue

8

Start / End Page

638

Related Subject Headings

  • Signal Transduction
  • Receptors, Androgen
  • RNA, Long Noncoding
  • Prostatic Neoplasms, Castration-Resistant
  • Prostatic Neoplasms
  • Phenylthiohydantoin
  • Nitriles
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice