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

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abstract

  • Significance TRAIL (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.

authors

  • Jeon, Young-Jun
  • Middleton, Justin
  • Kim, Taewan
  • Laganà, Alessandro
  • Piovan, Claudia
  • Secchiero, Paola
  • Nuovo, Gerard J
  • Cui, Ri
  • Joshi, Pooja
  • Romano, Giulia
  • Di Leva, Gianpiero
  • Lee, Bum-Kyu
  • Sun, Hui-Lung
  • Kim, Younggy
  • Fadda, Paolo
  • Alder, Hansjuerg
  • Garofalo, Michela
  • Croce, Carlo M

publication date

  • June 30, 2015