MicroRNA 101 Attenuated NSCLC Proliferation through IDH2/HIF alpha Axis Suppression in the Warburg Effect

Lung cancer is the most diagnosed and deadly cancer in China. MicroRNAs are small noncoding RNA gene products that exhibit multifunctional regulation in cancer cell progressions. MiR-101 loss was illustrated in about 29% of lung cancer patients, and sophisticated mechanisms of miR-101 regulation in NSCLC are eager to be disclosed. Here, using specimens from NSCLC patients and Dural-luciferase reporter assay, we got a clue that miR-101 correlated with IDH2. MiR-101 overexpression and IDH2 deficiency both suppressed NSCLC tumor growth in mice. Moreover, in NSCLC, miR-101 suppressed IDH2 expression levels, further increased alpha-KG concentration, and finally inhibited the Warburg effect under hypoxic conditions through downregulating HIF1 alpha expression by promoting HIF1 alpha hydroxylation and degradation. In conclusion, miR-101 attenuated the Warburg effect and NSCLC proliferation through IDH2/HIF1 alpha pathway.