Abstract
Mesenchymal stromal cells (MSCs) play an important role in the development of human cancer. Meanwhile, exosomes released by MSCs can mediate cell–cell communication by delivering microRNAs (miRNAs/miRs). Hence, this study aimed to explore the role of bone marrow mesenchymal stromal cell (BMSC)-derived exosomal miR-551b-3p in breast cancer. In this study, we found that upregulation of miR-551b-5p suppressed the proliferation and migration and induced the apoptosis of breast cancer cells via downregulating tripartite motif-containing protein 31 (TRIM31). In addition, miR-551b-5p could be transferred from BMSCs to breast cancer cells via exosomes; BMSC-derived exosomal miR-551b-3p suppressed the proliferation and migration and promoted the apoptosis and oxidative stress of MDA-MB-231 cells via inhibiting TRIM31. Furthermore, a xenograft mouse model was used to explore the role of BMSC-derived exosomal miR-551b-3p in vivo. We found that BMSC-derived exosomal miR-551b-3p inhibited tumor growth in a mouse xenograft model of breast cancer in vivo. Collectively, these findings indicated that BMSC-derived exosomal miR-551b-3p could suppress the development of breast cancer via downregulating TRIM31. Thus, miR-551b-3p could serve as a potential target for the treatment of breast cancer.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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The present study was supported by the Shanghai Pujiang Talent Program (Grant no. 18PJD005).
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ZY, BX and SW made major contributions to the conception and design of this study, and drafted the manuscript. WY, RL, SG, ZX, WJ, XS, XG and HZ were responsible for data acquisition, analysis and interpretation, and manuscript revision. HW made substantial contributions to the conception and design of the study and revised the manuscript. All authors agreed to be accountable for all aspects of the work. All authors read and approved the final manuscript.
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Both clinical and animal experiments have been approved by the Ethics Committee of the Zhongshan Hospital, Fudan University (No. Y2014-135). Written informed consent was obtained from all participants.
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13577_2022_753_MOESM1_ESM.tif
Supplementary file1 Figure. S1 Identification of DEMs in high-grade and low-grade breast cancer tissues. (A, B) Heat maps of DEMs in GSE131599 and TCGA. (C, D) Volcano plot of DEMs in GSE131599 and TCGA. DEMs, differentially expressed miRNAs; TCGA, The Cancer Genome Atlas (TIF 8346 KB)
13577_2022_753_MOESM2_ESM.tif
Supplementary file2 Figure. S2 miR-551b-3p inhibits the proliferation and migration of SK-BR-3 cells. (A) Reverse transcription-quantitative PCR analysis of miR-135a-5p, miR-551b-3p and miR-556-3p expression levels in MCF-10A and MDA-MB-231 cells. (B) SK-BR-3 cells were transfected with miR-551b-3p agomir or miR-551b-3p antagomir. Cell proliferation was detected via EdU staining. (C) Cell migration was measured by using a Transwell migration assay. **P<0.01. miR, microRNA (TIF 7370 KB)
13577_2022_753_MOESM3_ESM.tif
Supplementary file3 Figure. S3 miR-551b-3p inhibits the viability of breast cancer cells via negatively regulating TRIM31. MDA-MB-231 cells were transfected with miR-551b-3p agomir or/and TRIM31 siRNA2. Cell viability was detected via a Cell Counting Kit-8 assay. **P<0.01 (TIF 2196 KB)
13577_2022_753_MOESM4_ESM.tif
Supplementary file4 Figure. S4 Effects of BMSC-Exo on the proliferation and migration of breast cancer cells. (A) RT-qPCR analysis of miR-551b-3p expression levels in BMSCs, MCF-10A and MDA-MB-231 cells. (B) MDA-MB-231 cells were co-cultured with BMSCs. Meanwhile, MDA-MB-231 cells were treated with BMSC-Exo. RT-qPCR analysis of miR-551b-3p and TRIM31 expression levels in MDA-MB-231 cells. (C) Cell proliferation was detected via EdU staining. (D) Cell migration was measured by using a Transwell migration assay. **P<0.01. BMSCs, bone marrow mesenchymal stromal cells; BMSC-Exo, BMSC-derived exosomes; RT-qPCR, reverse transcription-quantitative PCR; miR, microRNA; TRIM31, tripartite motif-containing protein 31 (TIF 13371 KB)
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Yang, Z., Xu, B., Wu, S. et al. Exosomal microRNA-551b-3p from bone marrow-derived mesenchymal stromal cells inhibits breast cancer progression via regulating TRIM31/Akt signaling. Human Cell 35, 1797–1812 (2022). https://doi.org/10.1007/s13577-022-00753-x
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DOI: https://doi.org/10.1007/s13577-022-00753-x