ABSTRACT
Deregulated microRNAs (miRNAs) are small noncoding RNAs that are involved in the carcinogenesis of various cancers, including lung cancer. HIF1a has been suggested to be a master regulator of hypoxia-induced cell proliferation. The relationship between HIF1a expression and the progression of non-small cell lung cancer (NSCLC) is not fully understood, and whether HIF1a expression is regulated by miRNAs in this process remains unclear. In this study, we found that the upregulation of HIF1a expression and the reduction in miR-199a levels were highly associated with NSCLC progression. NSCLC cells derived from cancer tissues with low miR-199a levels showed high HIF1a expression and high proliferation capacity. Moreover, HIF1a and glycolysis inhibitors suppress the proliferation of NSCLC cells. MiR-199a overexpression suppressed the hypoxia-induced proliferation of NSCLC cells through targeting elevated HIF1a and blocking the downstream upregulation of PDK1 without affecting AKT activation. Together, these results indicate that downregulation of miR-199a is essential for hypoxia-induced proliferation through derepressing the expression of HIF1a expression and affecting HIF1a mediated glycolytic pathway in NSCLC progression.
