Exposure to desflurane anesthesia confers colorectal cancer cells metastatic capacity through deregulation of miR-34a/LOXL3

Colorectal Cancer
13/07/2020

Ren J, et al. Eur J Cancer Prev 2020.

ABSTRACT

Due to high potency and low toxicity, desflurane has been widely used during surgery. Recent evidence that the use of desflurane was associated with colorectal cancer (CRC) tumor metastasis and poor prognosis raising concerns about the safety of desflurane. However, the mechanism was uncovered. CRC cells were exposed to desflurane, the changes in morphology and epithelial-mesenchymal transition (EMT)-related genes were evaluated. Transwell assay was used to study the migration and invasion


effect. Xenograft was performed to study the tumor formation ability of desflurane-treated cells in vivo. Dual-luciferase reporter assay was conducted to verify the target of microRNA (miR)-34a. Knockdown or overexpression of LOXL3 was used to investigate the mechanism of desflurane-induced EMT. The association of LOXL3 with CRC molecular subtypes and clinical relevance was studied by analysis of public datasets. Exposure to desflurane induced EMT, migration, and invasion in CRC cells. Mice injected with desflurane-treated cells formed more tumors in the lungs. Downregulation of miR-34a and upregulation of LOXL3 were required for desflurane-induced EMT in CRC cells. LOXL3 was a direct target of miR-34a. Overexpression of LOXL3 rescued miR-34a-repressed EMT after exposure to desflurane. Elevated expression of LOXL3 was enriched in CMS4 and CRIS-B subtypes. Patients with high expression of LOXL3 showed more lymph node metastasis, as well as poor survival. Desflurane induced EMT and metastasis in CRC through deregulation of miR-34a/LOXL3 axis. Clinical miR-34a mimic or inhibitor targeting LOXL3 might have a potential protective role when patients with CRC anesthetized by desflurane.