Molecular mechanism of S100P promotes hepatocellular carcinoma by regulating MYBL2-mediated transcription of AURKB

Hepatocellular carcinoma (HCC) progression involves the synergistic roles of S100P and AURKB. Using bioinformatics, molecular assays, and in vitro/vivo models, we show that S100P activates the RAGE/Ras/p-p38/NFκB pathway, upregulating MYBL2, which directly enhances AURKB transcription. Clinically, S100P correlates positively with AURKB expression and tumor immune suppression. HCC cells with low S100P expression showed significantly greater sensitivity to the AURKB inhibitor AZD1152-HQPA than control cells, with a 61% decrease in IC₅₀. This study reveals the S100P/MYBL2/AURKB axis as a key driver of HCC and a predictor of targeted therapy response, supporting precision treatment strategies.