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<p>This study delves into the regulatory mechanism of TRERNA1 in ferroptosis of non-small cell lung cancer (NSCLC) cells. TRERNA1, KAT6A, and PIK3CA are abundantly expressed in NSCLC tissues and cells. TRERNA1 is negatively correlated with ACSL4 but positively correlated with GPX4. TRERNA1 knockdown inhibits cell proliferation and promotes ferroptosis. Mechanistically, TRERNA1 interacts with KAT6A protein to promote KAT6A expression and nuclear ectopy. KAT6A acetylates H3K23, which in turn enhances the binding of TRIM24 to H3K23ac. Therefore, TRIM24 acts as a transcriptional activator to activate the transcription of PIK3CA and inhibit ferroptosis. Overexpression of KAT6A or PIK3CA alleviateS the promoting effect of TRERNA1 knockdown on ferroptosis of NSCLC cells. In conclusion, TRERNA1 represses ferroptosis in NSCLC via the KAT6A/H3K23ac/TRIM24-PIK3CA pathway, representing a promising therapeutic strategy for NSCLC.</p>

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TRERNA1-mediated acetylation represses ferroptosis of non-small cell lung cancer cells via the KAT6A/H3K23ac/TRIM24-PIK3CA pathway

  • 期刊论文

  • 发表日期：

    2026年6月24日

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  • Bobo Li,
  • Yulan Sun

摘要

This study delves into the regulatory mechanism of TRERNA1 in ferroptosis of non-small cell lung cancer (NSCLC) cells. TRERNA1, KAT6A, and PIK3CA are abundantly expressed in NSCLC tissues and cells. TRERNA1 is negatively correlated with ACSL4 but positively correlated with GPX4. TRERNA1 knockdown inhibits cell proliferation and promotes ferroptosis. Mechanistically, TRERNA1 interacts with KAT6A protein to promote KAT6A expression and nuclear ectopy. KAT6A acetylates H3K23, which in turn enhances the binding of TRIM24 to H3K23ac. Therefore, TRIM24 acts as a transcriptional activator to activate the transcription of PIK3CA and inhibit ferroptosis. Overexpression of KAT6A or PIK3CA alleviateS the promoting effect of TRERNA1 knockdown on ferroptosis of NSCLC cells. In conclusion, TRERNA1 represses ferroptosis in NSCLC via the KAT6A/H3K23ac/TRIM24-PIK3CA pathway, representing a promising therapeutic strategy for NSCLC.