Exosomal microRNA-506 inhibits biological activity of lung adenocarcinoma cells and increases sensitivity to cisplatin-based hyperthermia

• Published in: Cellular signalling 2022-12, Vol.100, p.110469, Article 110469
• Main Authors: Zhang, Kunming, Sun, Xiwen, Sun, Weikai, Wang, Meng, Han, Fushi
• Format: Article
• Language: English
• Subjects: ATPase family AAA domain-containing protein 2; Cisplatin-based hyperthermia; Exosome; Lung adenocarcinoma; MicroRNA-506; Phosphatidylinositol 3-kinase/protein kinase B signaling pathway
• ISSN: 0898-6568; 1873-3913; 1873-3913
• DOI: 10.1016/j.cellsig.2022.110469

Exosomal microRNAs (miRNAs) play a vital role in the occurrence and development of lung adenocarcinoma (LUAD). Based on the bioinformatics analyses, the current study sought to explore the effects of exosomal miR-506 on LUAD cell biology and the efficacy of cisplatin (CDDP)-based hyperthermia (HT). After sample preparation, we identified decreased miR-506 and elevated ATAD2. LUAD cells were subsequently transfected with miR-506 mimic, oe-ATAD2 and PI3K/AKT signaling pathway inhibitor LY294002 to analyze effects of the miR-506/ATAD2/PI3K/AKT axis on cell biological processes and chemoresistance. Effects of exosomal miR-506 on sensitivity of LUAD cells to CDDP-based HT were further assessed in a co-culture system of BMSC-derived exosomes and LUAD cells, which was also validated in tumor-bearing nude mice. miR-506 down-regulated ATAD2 to inhibit the PI3K/AKT signaling pathway, thereby inhibiting the malignant phenotypes of LUAD cells and augmenting LUAD cell sensitivity to CDDP-based HT. Further, BMSCs-derived exosomes harboring miR-506 sensitized LUAD cells to DDP/HT both in vitro and in vivo. Collectively, our findings revealed that exosomal miR-506 sensitized LUAD cells to CDDP-based HT by inhibiting ATAD2/PI3K/AKT signaling pathway, offering a potential therapeutic target for LUAD treatment. [Display omitted] •MiR-506 inhibits LUAD by decreasing ATAD2.•MiR-506 enhances the sensitivity of LUAD cells on CDDP-based HT.•MiR-506 inhibits ATAD2 to block the PI3K/AKT signaling pathway.•BMSC-exosome carried miR-506 inhibits tumorigenesis of LUAD in vivo.•This study provides a new theoretical basis for clinical treatment of LUAD.