Endoplasmic reticulum stress upregulate HYOU1 and mediates lenvatinib resistance in liver cancer through ERK/MAPK pathway

Abstract Endoplasmic reticulum stress (ERS) is commonly observed in liver cancer and is associated with drug sensitivity. Consequently, ERS-related genes may serve as targets for enhancing treatment sensitivity. This study analyzed RNA and proteomic sequencing data from induced and non-induced ERS and identified hypoxia-upregulated protein 1 (HYOU1) as an ERS-related gene. We confirmed that ERS regulated HYOU1 expression. Database and microarray analyses revealed that HYOU1 expression level was significantly higher in cancer tissues than in normal tissues ( P P HYOU1 knockdown and Western blot (WB) results, we have, for the first time, identified that HYOU1 activates the ERK/MAPK pathway. We show that ERS promotes resistance to lenvatinib, whereas HYOU1 knockdown increases sensitivity to lenvatinib. We believe that HYOU1 plays a crucial role in treating lenvatinib-resistant liver cancer.