Accessibility-guided targeting of NRF2-responsive long noncoding RNA NMRAL2P alters a distinct gene expression program and reduces non-small cell lung cancer proliferation

Accessibility-guided antisense targeting of NRF2-responsive lncRNA NMRAL2P reduces non-small cell lung cancer proliferation and increases cisplatin sensitivity.

• Why it matters: NRF2 activation supports NSCLC survival and therapy resistance, yet downstream effectors beyond redox control are not fully defined.
• What they did: Transcriptome profiling linked LOC344887/NMRAL2P to NRF2 activity across normal lung and lung adenocarcinoma and lung squamous carcinoma cells; accessible NMRAL2P regions from in-cell SHAPE-MaP guided antisense gapmer design.
• The result: NMRAL2P depletion inhibited NSCLC proliferation and increased cisplatin sensitivity, while altering a restricted gene program involving cell adhesion and MAPK signaling distinct from NRF2 depletion, with core NRF2 antioxidant targets largely unaffected.

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