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Exosomes miR-22-3p Derived from Mesenchymal Stem Cells Suppress Colorectal Cancer Cell Proliferation and Invasion by Regulating RAP2B and PI3K/AKT Pathway

Objective. Exosomes (exo) which contain proteins, microRNAs (miRNAs), and other bioactive substances can participate in intercellular signal transduction and material transport. Bone marrow mesenchymal stem cells (BMSCs) have a strong ability to produce exosomes. The purpose of this study was to obs...

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Published in:Journal of oncology 2021, Vol.2021, p.3874478-10
Main Authors: Wang, Yan, Lin, Changkun
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description Objective. Exosomes (exo) which contain proteins, microRNAs (miRNAs), and other bioactive substances can participate in intercellular signal transduction and material transport. Bone marrow mesenchymal stem cells (BMSCs) have a strong ability to produce exosomes. The purpose of this study was to observe the effect of hBMSCs-derived-exo miR-22-3p on proliferation and invasion of colorectal cancer (CRC) cells and to explore its mechanism. Methods. miR-22-3p and RAS oncogene family (RAP2B) expression was detected using qRT-PCR or Western blotting. Their interaction was confirmed by dual luciferase activity assay. Effects of miR-22-3p on cell proliferation and invasion were evaluated by CCK-8 and Transwell assay, respectively. Exosomes were extracted by the ultracentrifugation and identified through electron microscopy and Western blotting. Results. In CRC tissues and cells, downregulation of miR-22-3p and upregulation of RAP2B were observed. According to the analysis of dual luciferase activity, RAP2B was a target gene of miR-22-3p. In addition, miR-22-3p obviously repressed the cells proliferation and invasion via mediating RAP2B/PI3K/AKT pathway. Coculture experiments indicated that miR-22-3p derived from hBMSCs-exo had inhibition effects on SW480 cell proliferation and invasion. Conclusions. Collectively, miR-22-3p from hBMSCs-exo might impede CRC progression, which emphasized the potential of hBMSCs-exo-miR-22-3p as CRC treatment in the future.
doi_str_mv 10.1155/2021/3874478
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Exosomes (exo) which contain proteins, microRNAs (miRNAs), and other bioactive substances can participate in intercellular signal transduction and material transport. Bone marrow mesenchymal stem cells (BMSCs) have a strong ability to produce exosomes. The purpose of this study was to observe the effect of hBMSCs-derived-exo miR-22-3p on proliferation and invasion of colorectal cancer (CRC) cells and to explore its mechanism. Methods. miR-22-3p and RAS oncogene family (RAP2B) expression was detected using qRT-PCR or Western blotting. Their interaction was confirmed by dual luciferase activity assay. Effects of miR-22-3p on cell proliferation and invasion were evaluated by CCK-8 and Transwell assay, respectively. Exosomes were extracted by the ultracentrifugation and identified through electron microscopy and Western blotting. Results. In CRC tissues and cells, downregulation of miR-22-3p and upregulation of RAP2B were observed. According to the analysis of dual luciferase activity, RAP2B was a target gene of miR-22-3p. In addition, miR-22-3p obviously repressed the cells proliferation and invasion via mediating RAP2B/PI3K/AKT pathway. Coculture experiments indicated that miR-22-3p derived from hBMSCs-exo had inhibition effects on SW480 cell proliferation and invasion. Conclusions. Collectively, miR-22-3p from hBMSCs-exo might impede CRC progression, which emphasized the potential of hBMSCs-exo-miR-22-3p as CRC treatment in the future.</description><identifier>ISSN: 1687-8450</identifier><identifier>EISSN: 1687-8450</identifier><identifier>DOI: 10.1155/2021/3874478</identifier><identifier>PMID: 34239562</identifier><language>eng</language><publisher>Egypt: Hindawi</publisher><subject>Angiogenesis ; Apoptosis ; Cell growth ; Cellular signal transduction ; Colorectal cancer ; Genes ; Medical diagnosis ; Medical prognosis ; Metastasis ; Proteins ; Software ; Statistical analysis ; Stem cells ; Tumors</subject><ispartof>Journal of oncology, 2021, Vol.2021, p.3874478-10</ispartof><rights>Copyright © 2021 Yan Wang et al.</rights><rights>Copyright © 2021 Yan Wang and Changkun Lin.</rights><rights>COPYRIGHT 2021 John Wiley &amp; Sons, Inc.</rights><rights>Copyright © 2021 Yan Wang et al. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright © 2021 Yan Wang and Changkun Lin. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-d3e85aac35a23c329b67726fddaed73dbc55a82f501da627f206b8720b018ef63</citedby><cites>FETCH-LOGICAL-c504t-d3e85aac35a23c329b67726fddaed73dbc55a82f501da627f206b8720b018ef63</cites><orcidid>0000-0002-3554-8178 ; 0000-0002-7731-8100</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2548294732/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2548294732?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,4010,25734,27904,27905,27906,36993,36994,44571,53772,53774,74875</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34239562$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Yuchi, Alamgeer</contributor><contributor>Alamgeer Yuchi</contributor><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Lin, Changkun</creatorcontrib><title>Exosomes miR-22-3p Derived from Mesenchymal Stem Cells Suppress Colorectal Cancer Cell Proliferation and Invasion by Regulating RAP2B and PI3K/AKT Pathway</title><title>Journal of oncology</title><addtitle>J Oncol</addtitle><description>Objective. Exosomes (exo) which contain proteins, microRNAs (miRNAs), and other bioactive substances can participate in intercellular signal transduction and material transport. Bone marrow mesenchymal stem cells (BMSCs) have a strong ability to produce exosomes. The purpose of this study was to observe the effect of hBMSCs-derived-exo miR-22-3p on proliferation and invasion of colorectal cancer (CRC) cells and to explore its mechanism. Methods. miR-22-3p and RAS oncogene family (RAP2B) expression was detected using qRT-PCR or Western blotting. Their interaction was confirmed by dual luciferase activity assay. Effects of miR-22-3p on cell proliferation and invasion were evaluated by CCK-8 and Transwell assay, respectively. Exosomes were extracted by the ultracentrifugation and identified through electron microscopy and Western blotting. Results. In CRC tissues and cells, downregulation of miR-22-3p and upregulation of RAP2B were observed. According to the analysis of dual luciferase activity, RAP2B was a target gene of miR-22-3p. In addition, miR-22-3p obviously repressed the cells proliferation and invasion via mediating RAP2B/PI3K/AKT pathway. Coculture experiments indicated that miR-22-3p derived from hBMSCs-exo had inhibition effects on SW480 cell proliferation and invasion. Conclusions. Collectively, miR-22-3p from hBMSCs-exo might impede CRC progression, which emphasized the potential of hBMSCs-exo-miR-22-3p as CRC treatment in the future.</description><subject>Angiogenesis</subject><subject>Apoptosis</subject><subject>Cell growth</subject><subject>Cellular signal transduction</subject><subject>Colorectal cancer</subject><subject>Genes</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Proteins</subject><subject>Software</subject><subject>Statistical analysis</subject><subject>Stem cells</subject><subject>Tumors</subject><issn>1687-8450</issn><issn>1687-8450</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNp90s9v0zAUB_AIgdgY3DgjS1yQINQ_Yse5IJUwoNoQVTfOluO8tJkSu9hJR_8V_lrctUyFw0629T762s96SfKS4PeEcD6hmJIJk3mW5fJRckqEzFOZcfz4aH-SPAvhBmOR4UI8TU5YRlnBBT1Nfp__csH1EFDfLlJKU7ZGn8C3G6hR412PvkEAa1bbXnfoaoAeldB1AV2N67WHEFDpOufBDLFcamvA3wE0965rG_B6aJ1F2tZoZjc67A7VFi1gOXaxZJdoMZ3Tj3dgPmMXk-nFNZrrYXWrt8-TJ43uArw4rGfJj8_n1-XX9PL7l1k5vUwNx9mQ1gwk19owrikzjBaVyHMqmrrWUOesrgznWtKGY1JrQfOGYlHJnOIKEwmNYGfJh33ueqx6qA3YwetOrX3ba79VTrfq34ptV2rpNkpSJgWRMeDNIcC7nyOEQfVtMPEXtAU3BkU5x1QQhmmkr_-jN270NrYXVSZpkeXsSC11B6q1jYv3ml2omopCSJkVnDysJOPxeTyL6t1eGe9C8NDcN0aw2g2Q2g2QOgxQ5K-OP-Me_52YCN7uwaq1tb5tH477A3mTy34</recordid><startdate>2021</startdate><enddate>2021</enddate><creator>Wang, Yan</creator><creator>Lin, Changkun</creator><general>Hindawi</general><general>John Wiley &amp; 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Lin, Changkun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-d3e85aac35a23c329b67726fddaed73dbc55a82f501da627f206b8720b018ef63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Angiogenesis</topic><topic>Apoptosis</topic><topic>Cell growth</topic><topic>Cellular signal transduction</topic><topic>Colorectal cancer</topic><topic>Genes</topic><topic>Medical diagnosis</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>Proteins</topic><topic>Software</topic><topic>Statistical analysis</topic><topic>Stem cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Lin, Changkun</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>ProQuest Health &amp; 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Exosomes (exo) which contain proteins, microRNAs (miRNAs), and other bioactive substances can participate in intercellular signal transduction and material transport. Bone marrow mesenchymal stem cells (BMSCs) have a strong ability to produce exosomes. The purpose of this study was to observe the effect of hBMSCs-derived-exo miR-22-3p on proliferation and invasion of colorectal cancer (CRC) cells and to explore its mechanism. Methods. miR-22-3p and RAS oncogene family (RAP2B) expression was detected using qRT-PCR or Western blotting. Their interaction was confirmed by dual luciferase activity assay. Effects of miR-22-3p on cell proliferation and invasion were evaluated by CCK-8 and Transwell assay, respectively. Exosomes were extracted by the ultracentrifugation and identified through electron microscopy and Western blotting. Results. In CRC tissues and cells, downregulation of miR-22-3p and upregulation of RAP2B were observed. According to the analysis of dual luciferase activity, RAP2B was a target gene of miR-22-3p. In addition, miR-22-3p obviously repressed the cells proliferation and invasion via mediating RAP2B/PI3K/AKT pathway. Coculture experiments indicated that miR-22-3p derived from hBMSCs-exo had inhibition effects on SW480 cell proliferation and invasion. Conclusions. Collectively, miR-22-3p from hBMSCs-exo might impede CRC progression, which emphasized the potential of hBMSCs-exo-miR-22-3p as CRC treatment in the future.</abstract><cop>Egypt</cop><pub>Hindawi</pub><pmid>34239562</pmid><doi>10.1155/2021/3874478</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-3554-8178</orcidid><orcidid>https://orcid.org/0000-0002-7731-8100</orcidid><oa>free_for_read</oa></addata></record>
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subjects Angiogenesis
Apoptosis
Cell growth
Cellular signal transduction
Colorectal cancer
Genes
Medical diagnosis
Medical prognosis
Metastasis
Proteins
Software
Statistical analysis
Stem cells
Tumors
title Exosomes miR-22-3p Derived from Mesenchymal Stem Cells Suppress Colorectal Cancer Cell Proliferation and Invasion by Regulating RAP2B and PI3K/AKT Pathway
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