M2‑TAM‑derived exosomal miR‑491‑3p modulates UBE2D3 and promotes the proliferation, migration and invasion of lung cancer cells

作者：Qiang Zhang, Y X Sun, Yu Zhuang, Shiwei Xu, Mengxu Yao, Siyang Jiao, Qi Wang, Feng Shao, Xiaoying Zhang · 发表于：Oncology Reports · 年份：2026 · DOI：10.3892/or.2026.9164 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、interferon and immune responses

M2 tumor-associated macrophages (M2-TAMs) have been reported to promote tumor growth through exosome-dependent mechanisms.However, the exact role of exosomes derived from M2-TAMs (M2-TAM-Exos) in lung cancer progression remains unclear.In The present study, M2-like macrophages (IL-4/IL-13-polarized THP-1-derived macrophages) were shown to release exosomes that lung cancer cells effectively internalized.These exosomes markedly enhanced the proliferation, migration, and invasion of lung cancer cells, thereby promoting malignancy.Further analyses revealed that M2-like macrophage-derived exosomes contain high levels of microRNA (miR)-491-3p.In vitro and in vivo experiments confirmed miR-491-3p as an oncogenic miR, while its inhibition markedly reduced cancer cell aggressiveness.Additional experiments demonstrated that miR-491-3p suppressed UBE2D3 expression after entering lung cancer cells.Collectively, these findings suggest a model in which M2-like macrophages deliver miR-491-3p via exosomes to downregulate UBE2D3, facilitating lung cancer progression.