A KAT7-lncPVT1 positive feedback loop promotes lung cancer carcinogenesis and therapy resistance via H3K14ac/HDGF/PI3K/AKT Axis

Lung cancer is one of the most life-threatening malignant tumors. The progression of tumors driven by chemo-radiotherapy resistance is the primary determinant of poor clinical outcomes, highlighting the crucial need for mechanistic insights into resistance pathways. In this study, we uncover that Lysine Acetyltransferase 7 (KAT7) overexpression not only promotes non-small cell lung cancer (NSCLC) cell proliferation in vitro and tumor growth in vivo but also confers resistance to chemotherapy and radiotherapy, which has been previously underexplored in NSCLC. Mechanistically, KAT7 forms a positive feedback loop with long non-coding RNA PVT1 (lncPVT1) and regulates the H3K14ac/HDGF axis and PI3K/AKT signaling pathway. This study aims to elucidate the molecular mechanisms by which the mutual regulation of KAT7, lncPVT1, and HDGF drives the proliferation and chemo-radiotherapy resistance of NSCLC.