In our current study, we demonstrated that i) deregulation of miR-1, miR-206 and miR-31 contributes to the conversion of NFs to CAFs in lung cancer; ii) combination of miR-1, miR-206 and miR-31 reprograms NFs to CAFs through mediating FOXO3a/VEGFA/CCL2 signaling; and iii) modifying tumor microenvironment via targeting three miRNAs or CCL2/VEGFA significantly reduced tumor angiogenesis, TAMs accumulation, tumor growth and lung metastasis. The gene discussed is CCL2; the disease is lung cancer.