miRNA-221-3p derived from M2-polarized tumor-associated macrophage exosomes aggravates the growth and metastasis of osteosarcoma through SOCS3/JAK2/STAT3 axis.
Animals
Apoptosis
Cell Line, Tumor
Cell Proliferation
/ genetics
Exosomes
/ metabolism
Gene Expression Regulation, Neoplastic
Heterografts
Humans
Janus Kinase 2
/ metabolism
Male
Mice
Mice, Inbred BALB C
MicroRNAs
/ genetics
Osteosarcoma
/ genetics
STAT3 Transcription Factor
/ metabolism
Signal Transduction
/ genetics
Suppressor of Cytokine Signaling 3 Protein
/ metabolism
Tumor-Associated Macrophages
/ metabolism
JAK2
SOCS3
STAT3
exosome
miR-221-3p
osteosarcoma
tumor-associated macrophages
Journal
Aging
ISSN: 1945-4589
Titre abrégé: Aging (Albany NY)
Pays: United States
ID NLM: 101508617
Informations de publication
Date de publication:
13 08 2021
13 08 2021
Historique:
received:
07
01
2021
accepted:
21
07
2021
pubmed:
14
8
2021
medline:
13
1
2022
entrez:
13
8
2021
Statut:
ppublish
Résumé
Enhanced infiltration of M2-polarized tumor-associated macrophages (TAMs) is linked to osteosarcoma (OS) metastasis and growth. Here, we aim to explore a novel miR-221-3p shuttled by M2-TAM exosomes in the growth and metastasis of OS cells. THP-1 monocytes-derived M2-TAMs were induced by PMA/interleukin (IL)-4/IL-13 and then co-cultured with OS 143B and Saos2 cells. Overexpression or downregulation models of miR-221-3p were conducted to probe the impacts of exosome-derived M2-TAMs in OS cells. OS cell proliferative ability, colony formation, invasion, migration and apoptotic level were measured by the cell counting kit-8 (CCK-8) assay, colony formation, Transwell assay, and flow cytometry. Moreover, the SOCS3/JAK2/STAT3 axis in OS cells was testified by western blot, and a dual-luciferase reporter assay was conducted to confirm the link between miR-221-3p and SOCS3. OS cells enhanced M2 polarization of TAMs, which significantly promoted OS cells' viability, colony formation, migration, invasion, and reduced apoptosis. Moreover, the exosomes enriched by miR-221-3p from M2-polarized TAMs (M2-TAMs) also aggravated the malignant behaviors of OS cells. However, down-regulation of miR-221-3p brought about contrary results. Further, The exosomal miR-221-3p derived from M2-TAMs aggravates OS progression via modulating the SOCS3/JAK2/STAT3 axis.
Sections du résumé
BACKGROUND
Enhanced infiltration of M2-polarized tumor-associated macrophages (TAMs) is linked to osteosarcoma (OS) metastasis and growth. Here, we aim to explore a novel miR-221-3p shuttled by M2-TAM exosomes in the growth and metastasis of OS cells.
METHODS
THP-1 monocytes-derived M2-TAMs were induced by PMA/interleukin (IL)-4/IL-13 and then co-cultured with OS 143B and Saos2 cells. Overexpression or downregulation models of miR-221-3p were conducted to probe the impacts of exosome-derived M2-TAMs in OS cells. OS cell proliferative ability, colony formation, invasion, migration and apoptotic level were measured by the cell counting kit-8 (CCK-8) assay, colony formation, Transwell assay, and flow cytometry. Moreover, the SOCS3/JAK2/STAT3 axis in OS cells was testified by western blot, and a dual-luciferase reporter assay was conducted to confirm the link between miR-221-3p and SOCS3.
RESULTS
OS cells enhanced M2 polarization of TAMs, which significantly promoted OS cells' viability, colony formation, migration, invasion, and reduced apoptosis. Moreover, the exosomes enriched by miR-221-3p from M2-polarized TAMs (M2-TAMs) also aggravated the malignant behaviors of OS cells. However, down-regulation of miR-221-3p brought about contrary results. Further,
CONCLUSION
The exosomal miR-221-3p derived from M2-TAMs aggravates OS progression via modulating the SOCS3/JAK2/STAT3 axis.
Identifiants
pubmed: 34388111
pii: 203388
doi: 10.18632/aging.203388
pmc: PMC8386545
doi:
Substances chimiques
MIRN221 microRNA, human
0
MicroRNAs
0
SOCS3 protein, human
0
STAT3 Transcription Factor
0
Suppressor of Cytokine Signaling 3 Protein
0
Janus Kinase 2
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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