Bone remodeling can be interrupted by tumor cells which leads to an inappropriate balance of osteoblasts and osteoclasts. As the progenitors of osteoblasts, mesenchymal stem cells (MSCs) have been reported to exhibit an abnormal osteogenic differentiation potential in some cancer‑related bone lesions. However, the evidence is very limited in terms of the biological alterations of MSCs in the bone metastasis of non‑small cell lung cancers (NSCLC). We investigated the expression and function of miR‑139‑5p in MSC osteogenic differentiation in vitro in normal and NSCLC-exposed condition. Then, we compared the serum miR‑139‑5p in stage IV lung adenocarcinoma cancer patients with and without lytic bone metastasis. We found that MSCs exhibited a significant increase in miR‑139‑5p expression after exposure to osteogenic differentiation induction medium. However, Notch1, which was confirmed as a target of miR‑139‑5p by luciferase and western blot assays, showed a marked downregulated expression together with its pathway downstream factors during MSC osteogenesis. miR‑139‑5p positively regulated MSC osteogenic differentiation but this effect was abrogated significantly by Notch1 knockdown. After exposure to conditions of lung cancer cells A549 and L9981, MSCs exhibited significant downregulation of miR‑139‑5p expression and early osteogenic marker ALP activity. Furthermore, we demonstrated that the expression of serum miR‑139‑5p from lung adenocarcinoma patients with lytic bone metastasis was significantly lower compared to that in patients with metastases in other organs. The potential roles of miR‑139‑5p as a biomarker and treatment target in monitoring and controlling bone metastasis in lung cancer patients are worthy of being further explored.