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<p>Gastric cancer (GC) remains a leading cause of global cancer mortality, necessitating deeper molecular insights. This study identifies KIF15 as a key driver of GC progression through integrated analysis of TCGA data and experimental validation. KIF15 is significantly overexpressed in GC tissues and correlates with advanced tumor stage, metastasis, and poor prognosis. Functional assays demonstrate that KIF15 enhances cancer stem cell (CSC) properties, proliferation, migration, invasion, and cisplatin resistance in GC cells. Mechanistically, KIF15 interacts with peroxiredoxin 1 (PRDX1), stabilizing this antioxidant protein to reduce intracellular hydroperoxides and maintain mitochondrial function. Depletion of PRDX1 reverses KIF15-mediated oncogenic effects. Further investigation reveals Yin Yang 1 (YY1) as the upstream transcriptional activator of KIF15. YY1 directly binds the KIF15 promoter, and its overexpression elevates KIF15 expression. Rescue experiments confirm that YY1 promotes GC malignancy via the KIF15-PRDX1 axis. Crucially, YY1 also transcriptionally regulates PRDX1, forming a coordinated regulatory circuit. In vivo models corroborate that the YY1/KIF15/PRDX1 axis drives tumor growth, metastasis, and chemoresistance. Collectively, these findings establish a novel YY1-KIF15-PRDX1 signaling axis that induces mitochondrial ROS imbalance to facilitate GC progression, offering potential prognostic markers and therapeutic targets.</p>

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The YY1-KIF15-PRDX1 axis promotes gastric cancer progression by inducing mitochondrial ROS imbalance

  • 期刊论文

  • 发表日期：

    2026年3月30日

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  • Wenjie Li,
  • Bozhi Wu,
  • Haisheng Qian,
  • Guoxin Zhang,
  • Xiaoyong Wang,
  • Xuan Li

摘要

Gastric cancer (GC) remains a leading cause of global cancer mortality, necessitating deeper molecular insights. This study identifies KIF15 as a key driver of GC progression through integrated analysis of TCGA data and experimental validation. KIF15 is significantly overexpressed in GC tissues and correlates with advanced tumor stage, metastasis, and poor prognosis. Functional assays demonstrate that KIF15 enhances cancer stem cell (CSC) properties, proliferation, migration, invasion, and cisplatin resistance in GC cells. Mechanistically, KIF15 interacts with peroxiredoxin 1 (PRDX1), stabilizing this antioxidant protein to reduce intracellular hydroperoxides and maintain mitochondrial function. Depletion of PRDX1 reverses KIF15-mediated oncogenic effects. Further investigation reveals Yin Yang 1 (YY1) as the upstream transcriptional activator of KIF15. YY1 directly binds the KIF15 promoter, and its overexpression elevates KIF15 expression. Rescue experiments confirm that YY1 promotes GC malignancy via the KIF15-PRDX1 axis. Crucially, YY1 also transcriptionally regulates PRDX1, forming a coordinated regulatory circuit. In vivo models corroborate that the YY1/KIF15/PRDX1 axis drives tumor growth, metastasis, and chemoresistance. Collectively, these findings establish a novel YY1-KIF15-PRDX1 signaling axis that induces mitochondrial ROS imbalance to facilitate GC progression, offering potential prognostic markers and therapeutic targets.