Transcriptomics

Dataset Information

0

RNAseq of Mouse Embryonic Fibroblasts(MEFs) stimulated by IL-17


ABSTRACT: The IL-17 receptor adaptor molecule Act1, an RNA binding protein, plays a critical role in IL-17-mediated cancer progression. Here we report a novel mechanism for how IL-17/Act1 induces chemoresistance by modulating redox homeostasis through epitranscriptomic regulation of antioxidant RNA metabolism. Transcriptome-wide mapping of direct Act1-RNA interactions revealed that Act1 binds to the 5'UTR of antioxidant mRNAs and Wilms' tumor 1-associating protein (WTAP), a key regulator in m6A methyltransferase complex. Strikingly, Act1's binding sites are located in proximity to m6A modification sites, which allows Act1 to promote the recruitment of elF3G for cap-independent translation. Loss of Act1’s RNA binding activity or Wtap knockdown abolished IL-17-induced m6A modification and translation of Wtap and antioxidant mRNAs, indicating a feedforward mechanism of Act1-WTAP loop. We then developed antisense oligonucleotides (Wtap ASO) that specifically disrupts Act1’s binding to Wtap mRNA, abolishing IL-17/Act1-WTAP-mediated antioxidant protein production during chemotherapy. Wtap ASO substantially increased the antitumor efficacy of cisplatin, demonstrating a potential therapeutic strategy for chemoresistance.

ORGANISM(S): Mus musculus

PROVIDER: GSE263596 | GEO | 2024/06/06

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-06-06 | GSE263835 | GEO
2024-11-10 | GSE188521 | GEO
2017-08-21 | GSE86451 | GEO
2020-07-15 | PXD019020 | Pride
| PRJNA1099569 | ENA
2018-03-14 | GSE94148 | GEO
2021-01-30 | GSE165781 | GEO
2011-10-18 | E-GEOD-24873 | biostudies-arrayexpress
2011-10-19 | GSE24873 | GEO
2013-11-29 | E-GEOD-46705 | biostudies-arrayexpress