Journal
EMBO REPORTS
Volume 21, Issue 4, Pages -Publisher
WILEY
DOI: 10.15252/embr.201948467
Keywords
bladder cancer; chemo-sensitivity; circular RNA
Categories
Funding
- NIH [CA155477]
- National Natural Science Foundation of China [81572523, 81873626, 81902592]
- Hunan Province Funds for Distinguished Young Scientists of China [2016JJ1026]
- Hunan Province Key RD Program [2019SK2202]
- Xiangya Hospital Youth Fund [2018Q09]
Ask authors/readers for more resources
The androgen receptor (AR) has been linked to bladder cancer (BCa) progression, but if this involves circular RNAs (circRNAs) remains unclear. Here, we find that AR alters the levels of circRNA-FNTA (circFNTA) to increase BCa cell invasion and chemo-resistance. Mechanistically, AR represses the RNA editing gene ADAR2 via direct binding to its 5' promoter region to increase circFNTA levels, which then sponges the microRNA miR-370-3p to increase the expression of its host gene FNTA. This AR-mediated ADAR2/circFNTA/miR-370-3p/FNTA pathway then activates KRAS signaling to alter BCa cell invasion and chemo-sensitivity to cisplatin. A clinical BCa sample survey shows that circFNTA expression is elevated in BCa tissues, and results from a BCa mouse model indicate that depletion of circFNTA leads to the suppression of BCa metastases and increased cisplatin chemo-sensitivity. Together, based on our results using multiple BCa cell lines and an in vivo mouse model we suggest that targeting this newly identified AR/ADAR2/circFNTA/miR-370-3p/FNTA/KRAS axis may lead to the development of therapies to suppress BCa metastasis and to increase its chemo-sensitivity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available