Abstract
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 α-KG concentration, and finally inhibited the Warburg effect under hypoxic conditions through downregulating HIF1α expression by promoting HIF1α hydroxylation and degradation. In conclusion, miR-101 attenuated the Warburg effect and NSCLC proliferation through IDH2/HIF1α pathway.