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Status |
Public on Jun 24, 2022 |
Title |
Compound-induced NR5A1 circular RNA and aberrant multiple exon-skipping attenuate aberrant steroidogenesis |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Despite the intensive search for an effective drug to ameliorate excess steroid production, there are few pharmacological options, especially for diseases as steroid-producing adrenocortical cancers. While splice-modifying-compounds have pleiotropic effects including anticancer properties, none have been tested on abnormal steroidogenesis. Using H295R adrenocortical carcinoma cells, CX-4945 induced multiple exon skipping of the NR5A1 gene, the master regulator of steroidogenesis. The resulting exon-skipped NR5A1 proteins were non-functional when added-back to NR5A1 knocked down H295R cells. This eventually suppressed steroidogenesis and induced dysfunctional autophagy with progression to ER-stress-related apoptosis. Intriguingly, a circular RNA of NR5A1 exons (circNR5A1 ex2-4 RNA) not originating from the skipped exons, was induced. Transient expression of this circNR5A1 ex2-4 RNA induced the same multiple exon-skipped isoforms of the NR5A1 gene. This potential pharmacological control of NR5A1 aberrant multiple exon-skipping and interplay with its circNR5A1 RNA gives us a novel target for treating abnormal steroidogenesis in adrenocortical carcinomas.
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Overall design |
CX-4945-induced gene expression in H295R adrenocortical cancer cells was compared with solvent (DMSO) treated H295R cells.
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Contributor(s) |
Tanaka T, Ohe K, Horita Y, Harada Y, Yamasaki T, Abe I, Abe M, Nomiyama T, Kobayashi K, Enjoji M, Yanase T |
Citation missing |
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Submission date |
Jun 24, 2019 |
Last update date |
Jun 25, 2022 |
Contact name |
Kenji Ohe |
Organization name |
Fukuoka University
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Department |
Faculty of Pharmaceutical Sciences
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Street address |
8-19-1, Jyonan-ku, nanakuma
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City |
Fukuoka |
State/province |
Fukuoka |
ZIP/Postal code |
814-0180 |
Country |
Japan |
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Platforms (1) |
GPL23126 |
[Clariom_D_Human] Affymetrix Human Clariom D Assay [transcript (gene) version] |
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Samples (6)
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Relations |
BioProject |
PRJNA550353 |