Breast Cancer Stem Cells-derived Extracellular Vesicles Affect PPARG Expression by Delivering MicroRNA-197 in Breast Cancer Cells

  • Clin Breast Cancer. 2022 Jul;22(5):478-490. doi: 10.1016/j.clbc.2022.02.006.
Lin Li  1 ,  Youyi Xiong  1 ,  Nan Wang  1 ,  Mingzhi Zhu  1 ,  Yuanting Gu  2
Affiliations
  • 1. Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
  • 2. Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: [email protected].
PMID: 35279406 DOI: 10.1016/j.clbc.2022.02.006
Abstract

Background: Breast Cancer (BC) is the most frequently diagnosed Cancer in women, and over 90% of BC-related deaths are associated with metastasis. The effects of BC stem cells-derived extracellular vesicles (BCSCs-EVs) have been implicated in Cancer control. This work aims to probe to the relevance of BCSCs-EVs to liver metastases of BC cells and the molecules involved.

Methods: First, EVs were extracted from BCSCs for MDA-MB-231 and SUM149PT cell co-culture. The effects of BCSCs-EVs on the proliferation of BC cells in vitro and in vivo as well as liver metastasis were evaluated. Subsequently, we analyzed differentially expressed MicroRNAs (miRNAs) after BCSCs-EVs by MicroRNA microarray and had them verified by RT-qPCR. Bioinformatics analysis was conducted to analyze target mRNAs of miR-197. The binding relationship of miR-197 to PPARG mRNA was examined. Finally, MDA-MB-231 and SUM149PT cells co-cultured with BCSCs-EVs were treated with miR-197 inhibitor or a PPARG-specific agonist.

Results: BCSCs-EVs promoted the growth of MDA-MB-231 and SUM149PT cells in vitro and in vivo as well as liver metastasis. BCSCs-EVs increased the expression of miR-197 in MDA-MB-231 and SUM149PT cells, and miR-197 could target PPARG mRNA. BCSCs-EVs treatment inhibited the mRNA and protein expression of PPARG in cells, thereby activating epithelial-mesenchymal transition (EMT). Knockdown of miR-197 or activation of PPARG in BCSCs-EVs-treated cells significantly counteracted the promoting effect of BCSCs-EVs on BC cell growth and metastasis.

Conclusion: BCSCs-EVs facilitated EMT of BC cells by delivering miR-197 to BC cells and inhibiting PPARG expression, thereby promoting growth and metastasis of BC cells.

Keywords
Co-culture; Epithelial-mesenchymal transition; Liver metastasis; MicroRNA-based microarray; Tumor growth.
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