Down-regulation of lncRNA OGFRP1 induces autophagy and growth inhibition by AKT/mTOR signaling pathway in HCAECs.

Long noncoding RNAs (lncRNAs) have been found to play important roles in nearly all biological processes. However, the functions of the majority of LncRNAs are not fully clear. Here we evaluated the function of lncRNA OGFRP1, which has not been previously annotated, in human coronary artery endothelial cells (HCAECs). First, we knocked down lncRNA OGFRP1 in HCAECs by using siRNA transfection. qRT-PCR results indicated that siRNA1 and siRNA3 both had potent interference efficiencies. Next, by using CCK8 assay and clone formation assay, we found that siRNA3 transfection induced growth inhibition in HCAECs. Cell migration and invasion were also found to be inhibited in OGFRP1 silenced cells. Moreover, siRNA1 transfection further verified the inhibitory effects of lncRNA OGFRP1 knockdown on the proliferation, migration and invasion of HCAECs. Flow cytometry detection demonstrated that OGFRP1 knockdown induced cell cycle arrest and apoptosis. Western blot assay indicated that p70S6K and CyclinD1 were down-regulated by knockdown of OGFRP1. The intrinsic apoptosis pathway was activated in lncRNA OGFRP1 silenced cells, including increased Bax and Active-caspase 3 and decreased Bcl2. The expression of autophagy markers LC3 and Beclin1 was increased and p62 decreased, all of which indicated that cell autophagy was promoted by down-regulation of lncRNA OGFRP1. Mechanistic studies showed that lncRNA OGFRP1 inhibited the AKT/mTOR signaling pathway, including increasing phosphorylation level of AKT, mTOR and GSK3β. In conclusion, we find that down-regulation of lncRNA induces autophagy and inhibited the proliferation, migration and invasion by AKT/mTOR signaling pathway in HCAECs.