Recent research has verified that mesenchymal stromal/stem cells (MSCs) derived from bone marrow or adipose tissues can migrate toward a variety of tumors. In this study, we explored whether human gingival-derived MSCs (G-MSCs) can migrate toward tongue squamous cell carcinoma (TSCC) and evaluated the antitumor effect of engineered G-MSCs in expressing and delivering the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). An in vitro cell migration assay with Transwell plates showed that human G-MSCs can migrate toward TSCC cell lines (Tca8113 and Cal27). Then, human G-MSCs, as a type of cell-based vehicle, were transduced with full-length TRAIL and enhanced green fluorescent protein reporter genes by the lentivirus (LV) system (G-MSCs with full-length TRAIL; G-MSCFLT). Tca8113 and Cal27 were co-cultured with G-MSCFLT, respectively, to evaluate the function of G-MSCFLT on tumor cells in vitro. This resulted in G-MSCFLT's inducing a great number of tumor cell necrosis and apoptosis. Meanwhile, in vivo antitumor assays were performed by administering G-MSCFLT to nude mice locally and systematically (mixed injection with tumor cells and tail vein injection). This showed that G-MSCFLT can reduce or even inhibit TSCC growth regardless of the method of administration, especially when the mixed injection of tumor cells and G-MSCFLT was at a ratio of 1:1, which showed no tumor formation. Furthermore, this verified that G-MSCFLT migrated toward TSCC in quantity. These data emphasize the effectiveness of G-MSCs as a vehicle for cell-based gene therapy and the antitumor activity of TRAIL-expressing G-MSCs.

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The breast cancer stem cells contribute to the initiation, progression, recurrence, metastasis as well as resistance of breast cancer. However, the mechanisms underlying the maintenance of breast cancer stemness have not been fully understood. Materials and methods: TCGA and GEO data were used for measuring miR-520b expression in breast cancer tissues. Kaplan-meier analysis was used for determining the relationship between miR-520b expression level and the prognosis of patients. Genetic manipulation was performed by lentivirus system and miR-520b inhibitor was used for knockdown of miR-520b. qRT-PCR and Western blot were employed to determine the mRNA and protein levels, respectively. The stemness and EMT (Epithelial to mesenchymal transition) were assessed by sphereformation and transwell assay as well as the expression of the related markers. The target genes of miR-520b were identified using the online database starBase V3.0. Results: miR-520b is upregulated in cancer tissues of breast cancer patients and predicts poor prognosis. Upregulation of miR-520b was found in breast cancer stem cells. Ectopic expression of miR-520b promotes the stemness of the breast cancer cells, conversely, depletion of miR-520b attenuates the stemness of these cells. miR-520b positively regulates Hippo/YAP signaling pathway and overexpression of LAST2 abolished the effect of miR-520b on the stemness of breast cancer cells. Conclusion: miR-520b promotes the stemness of breast cancer patients by activating Hippo/YAP signaling via targeting LATS2.