Abstract

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.

Highlights

  • Breast cancer (BC), as the most common malignant tumor, is the leading cause of malignant cancer-related death in women worldwide (Sun et al, 2017; Bray et al, 2018)

  • In this study, we focused on the potential mechanism of miRNAs carried by human umbilical cord mesenchymal stem cells-derived exosomes in breast cancer (BC)

  • Bases on xenograft models in nude mice, it was revealed that miR-224-5p carried by Human umbilical cord mesenchymal stem cells (hUCMSCs)-exo could regulate autophagy and contribute to the occurrence and development of BC in vivo

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Summary

Introduction

Breast cancer (BC), as the most common malignant tumor, is the leading cause of malignant cancer-related death in women worldwide (Sun et al, 2017; Bray et al, 2018). Among malignant tumors in Chinese women, its incidence ranks first and its mortality is second only to lung cancer (Waks and Winer, 2019), which seriously affects health and life of women. With the continuous improvement of diagnosis and treatment techniques of BC, its mortality still has no significant downward trend (Dihge et al, 2019). Malignant transformation of tumor cells involves multiple functional programming during which a number of gene products of therapeutic significance are induced, which can be used as molecular biomarkers and therapeutic targets to develop novel multi-target strategies to improve current cancer therapies and prevent disease recurrence (Mimeault and Batra, 2014). A large number of scholars continuously search for molecular indicators for early diagnosis of BC, molecular targets for its treatment and molecular markers for judging its prognosis

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