Silencing of MicroRNA-503 in Rat Mesenchymal Stem Cells Exerts Potent Antitumorigenic Effects in Lung Cancer Cells

Purpose: Mesenchymal stem cells (MSCs) are largely studied for their potential clinical use. Recently, there has been gained further interest in the relationship between MSCs and tumorigenesis. MSCs are reported to both promote and abrogate tumor growth. The present study was designed to investigate whether miRNAs are involved in the interactions between MSCs and tumor cells in the tumor microenvironment.

Materials And Methods: Rat bone marrow-derived MSCs (rMSCs) were cultured with or without tumor-conditioned medium (TCM) to observe the effect upon MSCs by TCM. Microarrays and real-time PCR were performed between the two groups. A series of experiments were used to reveal the functional significance of microRNA-503 (miR-503) in rMSCs. Furthermore, the antitumorigenic effect of silencing of miR-503 in rMSCs (miR-503-i-rMSCs) in vivo was measured.

Results: We found that rMSCs in vitro exhibited tumor-promoting properties in TCM, and the microRNA profiles of rMSCs were significantly altered in TCM. However, miR-503-i-rMSCs can decrease the angiogenesis and growth of A549 cells. We also demonstrated in an in vivo tumor model that miR-503-i-rMSCs inhibited A549 tumor angiogenesis and significantly abrogated tumor initiation and growth. CD133 assays in peripheral blood and A549 xenografts further validated that miR-503-i-rMSCs, rather than rMSCs, exerted an antitumorigenic action in the A549 tumor model.

Conclusion: Our results suggest that miR-503-i-rMSCs are capable of tumor suppression. Further studies are required to develop clinical therapies based on the inhibition of the tumor-promoting properties and potentiation of the anti-tumor properties of MSCs.