1. Academic Validation
  2. Exosomal microRNA-506 inhibits biological activity of lung adenocarcinoma cells and increases sensitivity to cisplatin-based hyperthermia

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

  • Cell Signal. 2022 Sep 14;100:110469. doi: 10.1016/j.cellsig.2022.110469.
Kunming Zhang 1 Xiwen Sun 2 Weikai Sun 3 Meng Wang 3 Fushi Han 4
Affiliations

Affiliations

  • 1 Department of Internal Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China.
  • 2 Department of Medical Imaging, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, PR China.
  • 3 Department of Radiotherapy, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China.
  • 4 Department of Nuclear Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China. Electronic address: hanfushi@tongji.edu.cn.
Abstract

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.

Keywords

ATPase family AAA domain-containing protein 2; Cisplatin-based hyperthermia; Exosome; Lung adenocarcinoma; MicroRNA-506; Phosphatidylinositol 3-kinase/protein kinase B signaling pathway.

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