- Qi R, Huang J, Wang Q, Liu H, Wang R, Wang J, Yang F. (2017) MicroRNA-224-5p regulates adipocyte apoptosis induced by TNFα via controlling NF-κB activation. Journal of Cellular Physiology 233(2):1236-1246.
Tumor necrosis factor (TNFα) can induce cell apoptosis and activate nuclear transcription (NF)-κB in different cell types. Activated NF-κB further promotes or suppresses cellular apoptosis in different cases. The present study explored the effect of activated NF-κB on adipocyte apoptosis induced by TNFα and which microRNAs (miRNAs) were involved in the process. Our findings demonstrated that treatment of differentiated 3T3-L1 adipocytes with TNFα (20ng/mL) rapidly activated NF-κB and induced moderate apoptosis. Pyrrolidinedithiocarbamic acid (PDTC, 60µM), a specific NF-κB inhibitor, abated NF-κB activation that rendered the adipocytes vulnerable to TNFα-induced apoptosis. Dozens of miRNAs exhibited significant expression changes following TNFα treatment and the addition of PDTC. In which, miRNA-224-5p (miR-224) was up-regulated by TNFÎ± exposure but down-regulated by PDTC addition. Furthermore, over-expression of miR-224 promoted NF-κB activation and prevented the adipocyte apoptosis induced by TNFα while miR-224 deficiency showed the opposite effects. The TRAF-associated NF-κB activator (TANK) gene was identified as a direct target of miR-224 by computational and luciferase reporter assays. Additionally, silencing the TANK gene by the small interfering RNA similarly promoted NF-ÎºB activation and attenuated the cellular apoptosis. In conclusion, these findings demonstrate that miR-224 plays an essential role in adipocyte apoptosis caused by TNFαthrough control of NF-κB activation via targeting the TANK gene.