Cancer-associated mesenchymal stem cell exosomes facilitate non-small cell lung cancer cell viability and invasiveness by delivering miR-182 in a FBXW7-related AKT and ERK-dependent pathway

Cancer-associated mesenchymal stem cells (CA-MSCs) modulate the tumor microenvironment and promote tumor progression. The present study aimed to investigate the effects of CA-MSCs, CA-MSC-derived exosomes and CA-MSC exosome-derived MicroRNA (miR)-182 on non-small cell lung Cancer (NSCLC) cell viability and invasiveness. CA-MSCs were established by treating MSCs with supernatant from NSCLC cells. Then, two NSCLC cell lines (A549 and H1299) were treated with CA-MSCs, CA-MSCs + GW4869 (inhibits exosomes) and CA-MSC exosomes. Additionally, miR-182 inhibitor was added to CA-MSCs and the related exosomes were used to treat NSCLC cells. Furthermore, miR-182 mimic and F-box and WD repeat domain containing 7 (FBXW7) overexpression vector were used to treat NSCLC cells. The results indicated that CA-MSCs promoted NSCLC cell viability and invasiveness and inhibited cell Apoptosis, an effect that was attenuated following GW4869 treatment. The CA-MSC exosomes also enhanced NSCLC cell viability and invasiveness while inhibiting cell Apoptosis. In addition, CA-MSC exosomes elevated miR-182 expression in NSCLC cells. Subsequently, CA-MSC exosomes with miR-182 expression knockdown exhibited a weakened effect on NSCLC cell viability, Apoptosis and invasiveness compared with control CA-MSC exosomes. Direct miR-182 mimic transfection enhanced NSCLC cell viability and invasiveness and inhibited cell Apoptosis, an effect that was attenuated by transfection with the FBXW7 overexpression vector. Furthermore, miR-182 negatively regulated and sponged FBXW7 expression in NSCLC cells. Finally, treatment of the cells with miR-182 mimic increased the phosphorylated (p-)Akt and p-ERK1/2 expression levels, while treatment with the FBXW7 overexpression vector decreased these levels in NSCLC cells. In summary, CA-MSCs facilitated NSCLC viability and invasiveness via transmitting exosomal miR-182 in a FBXW7-related Akt and ERK-dependent pathway.

F-box and WD repeat domain containing 7; cancer-associated mesenchymal stem cells; exosomes; lung cancer; microRNA-182.