miR-383 increases the cisplatin sensitivity of lung adenocarcinoma cells through inhibition of the RBM24-mediated NF-κB signaling pathway

The expression of microRNA-383 (miR-383) is downregulated in a variety of tumor tissues, and it exhibits antiproliferative activity in non-small cell lung cancer cells. In the present study, an association between the downregulation of miR-383 expression and the deletion of chr8p22 in patients with lung adenocarcinoma was identified. The promoting effect of miR-383 on cisplatin sensitivity was verified both in vivo and in vitro. Additionally, it was revealed that the expression of RNA binding motif protein 24 (RBM24) protein was regulated by and negatively correlated with miR-383 expression. Ectopic expression of RBM24 or inhibition of miR-383 decreased the chemosensitivity of parental A549 cells, whereas knockdown of RBM24 in cisplatin-resistant A549 cells increased chemosensitivity. Mechanistically, miR-383 interfered with the activation of nuclear factor kappa B (NF-kappa B) signaling through repression of RBM24-mediated phosphorylation of Rel-like domain-containing protein A and inhibitor alpha of NF-kappa B. Taken together, the downregulation of miR-383 induced RBM24 expression, which was mediated through the activation of NF-kappa B signaling, to contribute to chemotherapy resistance in lung adenocarcinoma cells. The results of the present study highlight potential therapeutic targets for the clinical reversal of the chemotherapy resistance in lung adenocarcinoma.

Automated summary

The downregulation of miR-383 leads to increased expression of RBM24 protein in lung adenocarcinoma cells, which activates chemotherapy resistance through NF-kappa B signaling pathway. The study provides potential therapeutic targets for clinical reversal of chemotherapy resistance in lung adenocarcinoma.