M2 macrophage-derived exosomal miR-1911-5p promotes cell migration and invasion in lung adenocarcinoma by down-regulating CELF2-activated ZBTB4 expression

Abstract

Lung adenocarcinoma (LUAD) is one of the most aggressive, lethal cancers, comprising around 40% of lung cancer cases. Metastases are the primary cause of LUAD deaths. The mechanism underlying metastatic LUAD and tumor microenvironment remain largely unknown. To explore the effect of M2 macrophage-derived exosomes on LUAD progression. Quantitative-PCR (q-PCR) and western blot were used to measure the expression of RNAs and proteins separately. Co-culture experiments wound healing and Transwell invasion assays were performed to evaluate the effect of M2 macrophage-derived exosomes on LUAD cell migration and invasion. RNA pulldown and luciferase reporter, RNA-binding immunoprecipitation (RIP), and mRNA stability assays were conducted to explore the downstream mechanism of exosomal microRNA-1911-5p (miR-1911-5p). M2 macrophage-derived exosomes accelerated the migration and invasion of LUAD cells. M2 macrophages-secreted exosomal miR-1911-5p enhanced cell migration and invasion in LUAD. Mechanically, miR-1911-5p targeted CUGBP- and ETR-3-like family 2 (CELF2) to downregulate zinc finger and BTB domain containing 4 (ZBTB4) in LUAD. Additionally, miR-1911-5p promoted LUAD progression via ZBTB4. The present study demonstrated that M2 macrophage-derived exosomal miR-1911-5p facilitates the migration and invasion of LUAD cells by inhibiting CELF2-activated ZBTB4, which might offer insight into LUAD treatment.

Exosomes: efficient macrophage-related immunomodulators in chronic lung diseases

“…Second, TAMs also contribute to the invasion and metastasis of lung cancer cells through exosomes. For example, exosomes derived from M2 macrophages containing miR-1911-5p facilitate the migration and invasion of lung adenocarcinoma cells by silencing zinc finger and BTB domain-containing 4 (ZBTB4) ( Guan et al, 2023 ), and ZBTB4 has been shown to regulate glycolipid metabolism and inhibit proliferation and invasion in malignancies such as pancreatic adenocarcinoma ( Yang et al, 2023 ) and glioma ( Dong et al, 2021 ). In lung cancer, ZBTB4 is also a target of CS-induced EMT ( Cheng et al, 2021 ).…”