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Small Extracellular Vesicles from adipose-derived stem cells suppress cell proliferation by delivering the let-7 family of microRNAs in ovarian cancer

Suzuki, Hironori ; Yokoi, Akira ; Uno, Kaname LU orcid ; Yoshida, Kosuke ; Kitagawa, Masami ; Asano-Inami, Eri ; Matsuo, Seiko ; Nagao, Yukari ; Suzuki, Kazuhiro and Nakamura, Kae , et al. (2023) In Biochemical and Biophysical Research Communications 680. p.211-219
Abstract

Introduction: Ovarian cancer is the leading cause of death among women with gynecological cancer, and novel treatment options are urgently needed. Extracellular vesicles (EVs), including exosomes, may be one of the most promising therapeutic tools for various diseases. In this study, we aimed to investigate the therapeutic effects of adipose-derived stem cell-derived EVs (ADSC-EVs) on ovarian cancer cell lines. Materials and methods: ADSCs and the ovarian cancer cell lines SKOV3 and OV90 were used for analysis. ADSC-EVs were isolated through ultracentrifugation and validated using a cryotransmission electron microscope, nanoparticle tracking analysis, and western blotting. Then, the effect of ADSC-EVs on ovarian cancer cells was... (More)

Introduction: Ovarian cancer is the leading cause of death among women with gynecological cancer, and novel treatment options are urgently needed. Extracellular vesicles (EVs), including exosomes, may be one of the most promising therapeutic tools for various diseases. In this study, we aimed to investigate the therapeutic effects of adipose-derived stem cell-derived EVs (ADSC-EVs) on ovarian cancer cell lines. Materials and methods: ADSCs and the ovarian cancer cell lines SKOV3 and OV90 were used for analysis. ADSC-EVs were isolated through ultracentrifugation and validated using a cryotransmission electron microscope, nanoparticle tracking analysis, and western blotting. Then, the effect of ADSC-EVs on ovarian cancer cells was investigated using IncuCyte and microRNA sequencing. Moreover, the potential functions of miRNAs were evaluated by gain-of function analysis and in silico analysis. Results: ADSC-EVs suppressed SKOV3 and OV90 cell proliferation. In particular, small EVs (sEVs) from ADSCs exhibited a stronger antitumor effect than ADSC-medium/large EVs (m/lEVs). Comparison of the miRNA profiles between ADSC-sEVs and ADSC-m/lEVs, along with downstream pathway analysis, suggested the involvement of the let-7 family. Overexpression of hsa-let-7b-5p and hsa-let-7e-5p significantly suppressed the proliferation of SKOV3 cells. In silico analysis revealed that four potential target genes of hsa-let-7b-5p and hsa-let-7e-5p were significantly associated with the prognoses of the patients. Conclusion: ADSC-sEVs had a stronger antitumor effect than ADSC-m/lEVs. Hsa-let-7b-5p and hsa-let-7e-5p, which are highly abundant in ADSC-sEVs, suppressed cell proliferation. These findings may open up new possibilities for therapeutic approaches using ADSC-sEVs.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
hsa-let-7b-5p, hsa-let-7e-5p, Medium/large extracellular vesicles, Ovarian cancer, Small extracellular vesicles
in
Biochemical and Biophysical Research Communications
volume
680
pages
9 pages
publisher
Elsevier
external identifiers
  • pmid:37782986
  • scopus:85172674502
ISSN
0006-291X
DOI
10.1016/j.bbrc.2023.09.022
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 Elsevier Inc.
id
ecb73398-ed17-45da-9b8f-9acdfb8dab85
date added to LUP
2023-12-04 15:02:00
date last changed
2024-05-01 12:25:42
@article{ecb73398-ed17-45da-9b8f-9acdfb8dab85,
  abstract     = {{<p>Introduction: Ovarian cancer is the leading cause of death among women with gynecological cancer, and novel treatment options are urgently needed. Extracellular vesicles (EVs), including exosomes, may be one of the most promising therapeutic tools for various diseases. In this study, we aimed to investigate the therapeutic effects of adipose-derived stem cell-derived EVs (ADSC-EVs) on ovarian cancer cell lines. Materials and methods: ADSCs and the ovarian cancer cell lines SKOV3 and OV90 were used for analysis. ADSC-EVs were isolated through ultracentrifugation and validated using a cryotransmission electron microscope, nanoparticle tracking analysis, and western blotting. Then, the effect of ADSC-EVs on ovarian cancer cells was investigated using IncuCyte and microRNA sequencing. Moreover, the potential functions of miRNAs were evaluated by gain-of function analysis and in silico analysis. Results: ADSC-EVs suppressed SKOV3 and OV90 cell proliferation. In particular, small EVs (sEVs) from ADSCs exhibited a stronger antitumor effect than ADSC-medium/large EVs (m/lEVs). Comparison of the miRNA profiles between ADSC-sEVs and ADSC-m/lEVs, along with downstream pathway analysis, suggested the involvement of the let-7 family. Overexpression of hsa-let-7b-5p and hsa-let-7e-5p significantly suppressed the proliferation of SKOV3 cells. In silico analysis revealed that four potential target genes of hsa-let-7b-5p and hsa-let-7e-5p were significantly associated with the prognoses of the patients. Conclusion: ADSC-sEVs had a stronger antitumor effect than ADSC-m/lEVs. Hsa-let-7b-5p and hsa-let-7e-5p, which are highly abundant in ADSC-sEVs, suppressed cell proliferation. These findings may open up new possibilities for therapeutic approaches using ADSC-sEVs.</p>}},
  author       = {{Suzuki, Hironori and Yokoi, Akira and Uno, Kaname and Yoshida, Kosuke and Kitagawa, Masami and Asano-Inami, Eri and Matsuo, Seiko and Nagao, Yukari and Suzuki, Kazuhiro and Nakamura, Kae and Yoshihara, Masato and Tamauchi, Satoshi and Shimizu, Yusuke and Ikeda, Yoshiki and Yoshikawa, Nobuhisa and Kajiyama, Hiroaki and Yamamoto, Yusuke}},
  issn         = {{0006-291X}},
  keywords     = {{hsa-let-7b-5p; hsa-let-7e-5p; Medium/large extracellular vesicles; Ovarian cancer; Small extracellular vesicles}},
  language     = {{eng}},
  month        = {{11}},
  pages        = {{211--219}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical and Biophysical Research Communications}},
  title        = {{Small Extracellular Vesicles from adipose-derived stem cells suppress cell proliferation by delivering the let-7 family of microRNAs in ovarian cancer}},
  url          = {{http://dx.doi.org/10.1016/j.bbrc.2023.09.022}},
  doi          = {{10.1016/j.bbrc.2023.09.022}},
  volume       = {{680}},
  year         = {{2023}},
}