miR-660-5p-loaded M2 macrophages-derived exosomes augment hepatocellular carcinoma development through regulating KLF3

•miR-660-5p is up-regulated while KLF3 is down-regulated in HCC.•M2-Exo promote the development of HCC.•KLF3 has a targeting relationship with miR-660-5p.•miR-660-5p-loaded M2-Exo promote HCC development.•Elevating KLF3 impairs HCC progression mediated by miR-660-5p-modified M2-Exo. M2 macrophages (M2) can affect tumor development by secreting various cytokines, including exosomes (Exo). Herein, we intended to explore how microRNA (miR)-660-5p-modified M2-Exo affected hepatocellular carcinoma (HCC) development through regulating Kruppel-like factor 3 (KLF3). miR-660-5p and KLF3 levels were first measured in clinical HCC tissues. A miR-targeted relation was explored between miR-660-5p and KLF3. M2-Exo were modified by miR-660-5p-related oligonucleotides and co-cultured with HepG2 cells to determine their effects on cell proliferation, colony formation, invasion, migration, apoptosis and epithelial-mesenchymal transition (EMT). Xenografted tumors were collected from mice to further verify the in vitro results. Higher miR-660-5p and lower KLF3 levels were examined in HCC. KLF3 was targeted by miR-660-5p. Up-regulated miR-660-5p-modified M2-Exo boosted the grwoth and EMT of HepG2 cells, but this effect was impaired by overexpression of KLF3. miR-660-5p-loaded M2-Exo enhanced tumorigenic ability of HCC cells in mice. On the contrary, down-regulated miR-660-5p reduced M2-Exo-mediated promotion of growth of HCC cells in vitro and in vivo. Our study summarizes that miR-660-5p-loaded M2-Exo augment HCC development through down-regulating KLF3.