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http://purl.uniprot.org/citations/33728488http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33728488http://www.w3.org/2000/01/rdf-schema#comment"

Aim

Given the fact that tumor-associated macrophage-derived extracellular vesicles (EVs) are attributable to tumor aggressiveness, this research intends to decode the mechanism of M2 macrophage-derived EVs in the differentiation and activities of pancreatic cancer (PaCa) stem cells via delivering microRNA (miR)-21-5p.

Methods

Polarized M2 macrophages were induced, from which EVs were collected and identified. miR-21-5p expression in M2 macrophage-derived EVs was tested. After cell sorting, CD24+CD44+EpCAM+ stem cells were co-cultured with M2 macrophages, in which miR-21-5p was upregulated or downregulated. The effects of M2 macrophage-derived EVs and miR-21-5p on Nanog/octamer-binding transcription factor 4 (Oct4) expression, sphere formation, colony formation, invasion and migration capacities, apoptosis, and in vivo tumorigenic ability were examined. Krüppel-like factor 3 (KLF3) expression and its interaction with miR-21-5p were determined.

Results

M2 macrophage-derived EVs promoted PaCa stem cell differentiation and activities. miR-21a-5p was upregulated in M2 macrophage-derived EVs. miR-21a-5p downregulation in M2 macrophage-derived EVs inhibited Nanog/Oct4 expression and impaired sphere-forming, colony-forming, invasion, migration, and anti-apoptosis abilities of PaCa stem cells in vitro and tumorigenic ability in vivo. miR-21-5p targeted KLF3 to mediate the differentiation and activities of PaCa stem cells, and KLF3 was downregulated in PaCa stem cells.

Conclusion

This work explains that M2 macrophage-derived exosomal miR-21a-5p stimulates differentiation and activity of PaCa stem cells via targeting KLF3, paving a novel way for attenuating PaCa stemness."xsd:string
http://purl.uniprot.org/citations/33728488http://purl.org/dc/terms/identifier"doi:10.1007/s10565-021-09597-x"xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/author"Chang J."xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/author"Hu W."xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/author"Li H."xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/author"Tao J."xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/author"Xiong X."xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/author"Zhu Z."xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/author"Mei P."xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/name"Cell Biol Toxicol"xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/pages"577-590"xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/title"microRNA-21-5p from M2 macrophage-derived extracellular vesicles promotes the differentiation and activity of pancreatic cancer stem cells by mediating KLF3."xsd:string
http://purl.uniprot.org/citations/33728488http://purl.uniprot.org/core/volume"38"xsd:string
http://purl.uniprot.org/citations/33728488http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33728488
http://purl.uniprot.org/citations/33728488http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33728488
http://purl.uniprot.org/uniprot/#_B2R8P9-mappedCitation-33728488http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33728488
http://purl.uniprot.org/uniprot/#_P57682-mappedCitation-33728488http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33728488
http://purl.uniprot.org/uniprot/P57682http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33728488
http://purl.uniprot.org/uniprot/B2R8P9http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33728488