The lncRNA DAMER selectively guides m6A-dependent regulation of ATF4 and asparagine metabolism under nutrient stress in cancer - PubMed
3 days ago
- #metabolic stress
- #lncRNA
- #cancer therapy
- The lncRNA DAMER guides m6A-dependent regulation of ATF4 and asparagine metabolism under nutrient stress in cancer.
- Glucose or glutamine deprivation induces endoplasmic reticulum stress, leading to NRF2-dependent transcription of DAMER.
- DAMER, demethylated and retained in the nucleus by ALKBH5, acts as a scaffold to stabilize ATF4 mRNA through base-pairing.
- This mechanism rewires asparagine metabolism to promote cancer cell survival under metabolic stress.
- Elbasvir, an FDA-approved drug, inhibits the DAMER-ALKBH5 interaction, disrupting this adaptive pathway and showing antitumour effects.
- The study reveals a lncRNA-guided RNA demethylation mechanism and offers a strategy to target metabolic adaptation in cancer.