Exosomes Derived From MicroRNA-148b-3p-Overexpressing Human Umbilical Cord Mesenchymal Stem Cells Restrain Breast Cancer Progression

AbstractBreast cancer is the leading cause of cancer-related death for women. In breast cancer treatment, targeted therapy would be more effective and less harmful than radiotherapy or systemic chemotherapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in cancer cells but not in normal cells. Mesenchymal stem cells have shown great therapeutic potential in cancer therapy owing to their ability of homing to tumor sites and secreting many kinds of anti-tumor proteins including TRAIL. In this study, we found that IL-1β-stimulated human umbilical cord-derived mesenchymal stem cells (hUCMSCs) enhance the expression of membrane-bound and soluble TRAIL. Cellular FADD-like IL-1β-converting enzyme inhibitory protein (cFLIP) is an important regulator in TRAIL-mediated apoptosis and relates to TRAIL resistance in cancer cells. Previous studies have shown that embelin, which is extracted from Embelia ribes, can increase the TRAIL sensitivity of cancer cells by reducing cFLIP expression. Here we have demonstrated that cFLIPL is correlated with TRAIL-resistance and that embelin effectively downregulates cFLIPL in breast cancer cells. Moreover, co-culture of IL-1β-stimulated hUCMSCs with embelin-treated breast cancer cells could effectively induce apoptosis in breast cancer cells. The combined effects of embelin and IL-1β-stimulated hUCMSCs may provide a new therapeutic strategy for breast cancer therapy.

Download Full-text

Human Umbilical Cord Matrix Mesenchymal Stem Cells Suppress the Growth of Breast Cancer by Expression of Tumor Suppressor Genes

PLoS ONE ◽

10.1371/journal.pone.0123756 ◽

2015 ◽

Vol 10 (5) ◽

pp. e0123756 ◽

Cited By ~ 11

Author(s):

Naomi Ohta ◽

Susumu Ishiguro ◽

Atsushi Kawabata ◽

Deepthi Uppalapati ◽

Marla Pyle ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tumor Suppressor ◽

Umbilical Cord ◽

Tumor Suppressor Genes ◽

Human Umbilical Cord ◽

Suppressor Genes ◽

Umbilical Cord Matrix

Download Full-text

miR-224-5p Carried by Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes Regulates Autophagy in Breast Cancer Cells via HOXA5

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.679185 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yichao Wang ◽

Pan Wang ◽

Lei Zhao ◽

Xiaoying Chen ◽

Zhu Lin ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Rna Binding ◽

Luciferase Reporter ◽

Human Umbilical Cord ◽

Luciferase Reporter Gene ◽

Gene Assay

Objective: In this study, we focused on the potential mechanism of miRNAs carried by human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-exo) in breast cancer (BC).Methods: RT-qPCR was conducted for the expression of miR-224-5p and HOXA5 in tissues and cells. After co-culture of exosomes and MCF-7 or MDA-MB-231 cells, the cell proliferation was observed by MTT and cell colony formation assay, while apoptosis was measured by flow cytometry. In addition, the expression of HOXA5 and autophagy pathway-related proteins LC3-II, Beclin-1 and P62 was detected by western blotting. And immunofluorescence was applied for detection of LC3 spots. The binding of miR-224-5p to HOXA5 was verified by the luciferase reporter gene assay and RNA-binding protein immunoprecipitation assay. Finally, in vivo experiment was performed to investigate the effect of miR-224-5p on BC growth.Results: MiR-224-5p was up-regulated and HOXA5 was down-regulated in BC tissues and cells. HOXA5 was confirmed to be the target gene of miR-224-5p. MiR-224-5p carried by hUCMSCs-exo was able to promote the proliferation and autophagy of BC cells, while inhibited apoptosis. Bases on xenograft models in nude mice, it was also revealed that miR-224-5p carried by hUCMSCs-exo could regulate autophagy and contribute to the occurrence and development of BC in vivo.Conclusion: MiR-224-5p carried by hUCMSCs-exo can regulate autophagy via inhibition of HOXA5, thus affecting the proliferation and apoptosis of BC cells.

Download Full-text