A set of NF-κB–regulated microRNAs induces acquired TRAIL resistance in Lung cancer

SignificanceTRAIL (TNF-related apoptosis-inducing ligand) is a promising antitumor agent effective in a very small subset of lung cancer patients with low toxicity. However, the majority of lung tumors are TRAIL-resistant and very little is known about how tumor cells acquire resistance to TRAIL. Here, we show that continuous exposure to subtoxic concentrations of TRAIL induces NF-κB–dependent up-regulation of miR-21, miR-30c, and miR-100, which by silencing caspase-8, caspase-3, TRAF7, and FoxO3a further strengthens the NF-κB signaling, inducing acquired TRAIL resistance. Our findings imply that combinatory therapies of NF-κB inhibitors and TRAIL might be a useful therapy to improve the response of lung cancer to TRAIL.

A set of NF-κB–regulated microRNAs induces acquired TRAIL resistance in Lung cancer Journal Articles