Suppressive function of bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-187 in prostate cancer

Cancer Biol Ther. 2022 Dec 31;23(1):1-14. doi: 10.1080/15384047.2022.2123675.

Abstract

Application of bone marrow-derived mesenchymal stem cell-derived exosomes (BMSC-exos) in cancer treatment has been widely studied. Here, we elaborated the function of BMSC-exos containing microRNA-187 (miR-187) in prostate cancer. Differentially expressed miRs and genes were screened with microarray analysis. The relationship between CD276 and miR-187 in prostate cancer was evaluated. Following miR-187 mimic/inhibitor or CD276 overexpression transfection, their actions in prostate cancer cell biological processes were analyzed. Prostate cancer cells were then exposed to BMSC-exos that were treated with either miR-187 mimic/inhibitor or CD276 overexpression for pinpointing the in vitro and in vivo effects of exosomal miR-187. miR-187 was poorly expressed while CD276 was significantly upregulated in prostate cancer. Additionally, restoring miR-187 inhibited the prostate cancer cell malignant properties by targeting CD276. Upregulation of miR-187 led to declines in CD276 expression and the JAK3-STAT3-Slug signaling pathway. Next, BMSC-exos carrying miR-187 contributed to repressed cell malignant features as well as limited tumorigenicity and tumor metastasis. Collectively, this study demonstrated that BMSC-derived exosomal miR-187 restrained prostate cancer by reducing CD276/JAK3-STAT3-Slug axis.

Keywords: CD276; JAK3-STAT3-Slug signaling pathway; Prostate cancer; exosomes; human bone marrow-derived mesenchymal stem cells; microRNA-187.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7 Antigens / metabolism
  • B7 Antigens / pharmacology
  • Bone Marrow / metabolism
  • Cell Proliferation / genetics
  • Exosomes* / metabolism
  • Humans
  • Male
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Prostatic Neoplasms* / pathology

Substances

  • B7 Antigens
  • CD276 protein, human
  • MIRN187 microRNA, human
  • MicroRNAs

Grants and funding

This work was supported by General Project of Chongqing Natural Science Foundation (No. cstc2021jcyj-msxmX0611), Chongqing Doctor “Through Train„ Scientific Research Project (CSTBBSXM2022-JCX0007)and National Natural Science Foundation of China (No. 81972411).