Cancer‑associated mesenchymal stem cell exosomes facilitate non‑small cell lung cancer cell viability and invasiveness&nbsp;<br />by delivering miR‑182 in a FBXW7‑related AKT and ERK‑dependent pathway

Sun,Yahong; Zhu,Xingxing; Yu,Lina; Dong,Hui; Liu,Zhihao

doi:10.3892/ol.2025.15233

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

Authors:
- Yahong Sun
- Xingxing Zhu
- Lina Yu
- Hui Dong
- Zhihao Liu
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Affiliations: Department of Respiratory and Critical Care Medicine, Haining People's Hospital, Haining, Zhejiang 314400, P.R. China
Published online on: August 19, 2025 https://doi.org/10.3892/ol.2025.15233
Article Number: 487
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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