HIF1? and HIF2? regulate non-small-cell lung cancer dedifferentiation via expression of Sox2 and Oct4 under hypoxic conditions

Objective: To explore HIF1 alpha and HIF2 alpha regulate the dedifferentiation of lung cancer cells under hypoxic conditions through Sox2 and Oct4. Materials and methods: HIF1 alpha, HIF2 alpha, Sox2 and Oct4 expression was analysed in lung cancer tissues. We analysed sphere formation by single-cell of differentiated lung cancer under hypoxia, and detected the expression of CD133, CD44, Sox2, Oct4, HIF1 alpha and HIF2 alpha. We knocked out HIF1 alpha, HIF2 alpha, Sox2 or Oct4 in cells, cultured the cells under hypoxic conditions and detected CD133 and CD44 using western blotting. We also detected the apoptosis rate of cells with HIF1 alpha, HIF2 alpha, Sox2 or Oct4 knockout. Results: There was more sphere formation of differentiated lung cancer cells under hypoxic conditions than of control cells under normoxic conditions. These newly formed spheres highly expressed CD133 and CD44. TCGA database showed high expression of HIF1 alpha and HIF2 alpha in lung cancer tissues. After knocking out HIF1 alpha and HIF2 alpha, the expression of Sox2, Oct4, CD133 and CD44 decreased significantly, and after knocking out Sox2 or Oct4, the expression of CD133 and CD44 decreased. Conclusion: HIF1 alpha and HIF2 alpha regulate non-small-cell lung cancer dedifferentiation through Sox2 and Oct4 under hypoxic conditions.

Automated summary

Objective: To investigate the role of HIF1 alpha and HIF2 alpha in regulating the dedifferentiation of lung cancer cells under hypoxic conditions through Sox2 and Oct4. Methods: The expression of HIF1 alpha, HIF2 alpha, Sox2, and Oct4 was analyzed in lung cancer tissues. Sphere formation and the expression of CD133, CD44, Sox2, Oct4, HIF1 alpha, and HIF2 alpha were examined in differentiated lung cancer cells cultured under hypoxia. Knockout experiments were performed for HIF1 alpha, HIF2 alpha, Sox2, and Oct4, and the effects on CD133 and CD44 expression were evaluated. Results: Differentiated lung cancer cells formed more spheres under hypoxic conditions and exhibited higher expression of CD133 and CD44. TCGA database analysis revealed elevated levels of HIF1 alpha and HIF2 alpha in lung cancer tissues. Knockout of HIF1 alpha and HIF2 alpha resulted in decreased expression of Sox2, Oct4, CD133, and CD44, while knockout of Sox2 or Oct4 led to decreased expression of CD133 and CD44. Conclusion: HIF1 alpha and HIF2 alpha play a crucial role in regulating the dedifferentiation of non-small-cell lung cancer cells through Sox2 and Oct4 under hypoxic conditions.