Upregulation of exosomal microRNA‑21 in pancreatic stellate cells promotes pancreatic cancer cell migration and enhances Ras/ERK pathway activity
Pancreatic stellate cells (PSCs) are typically activated in pancreatic ductal adenocarcinoma (PDAC) and release exosomes containing high levels of microRNA‑21 (miR‑21). However, the specific roles of exosomal miR‑21 in regulating the PDAC malignant phenotype remain unknown. The present study aimed t...
Gespeichert in:
| Veröffentlicht in: | International journal of oncology 2020-04, Vol.56 (4), p.1025-1033 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1033 |
|---|---|
| container_issue | 4 |
| container_start_page | 1025 |
| container_title | International journal of oncology |
| container_volume | 56 |
| creator | Ma, Qiang Wu, Huanwen Xiao, Ying Liang, Zhiyong Liu, Tonghua |
| description | Pancreatic stellate cells (PSCs) are typically activated in pancreatic ductal adenocarcinoma (PDAC) and release exosomes containing high levels of microRNA‑21 (miR‑21). However, the specific roles of exosomal miR‑21 in regulating the PDAC malignant phenotype remain unknown. The present study aimed to determine the effects of exosomal miR‑21 on the migratory ability of PDAC cells and explore the potential underlying molecular mechanism. Weighted gene correlation network and The Cancer Genome Atlas database analysis revealed that high miR‑21 levels were associated with a poor prognosis in patients with pancreatic adenocarcinoma, and that the Ras/ERK signaling pathway may be a potential target of miR‑21. In vitro, PDAC cells were demonstrated to internalize the PSC-derived exosome, resulting in high miR‑21 levels, which subsequently promoted cell migration, induced epithelial‑to‑mesenchymal transition (EMT) and increased matrix metalloproteinase‑2/9 activity. In addition, exosomal miR‑21 increased the levels of ERK1/2 and Akt phosphorylation in PDAC cells. Collectively, these results suggested that PSC‑derived exosomal miR‑21 may promote PDAC cell migration and EMT and enhance Ras/ERK signaling activity. Thus, miR‑21 may be a potential cause of poor prognosis in patients with pancreatic cancer and a new treatment target. |
| doi_str_mv | 10.3892/ijo.2020.4986 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_2371278886</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A619214941</galeid><sourcerecordid>A619214941</sourcerecordid><originalsourceid>FETCH-LOGICAL-c458t-dfb6f105472d50e0e04d48d1f898b9e17e23e149a02d4fd8e2e1b51c74b198983</originalsourceid><addsrcrecordid>eNptks1u1DAQxyMEoqVw5IosIXHL1nacxD6uqvIhKpBW9Gw5zmTXqyRebKewN14B8YY8CZNuPyU0hxnZv5mxZ_5Z9prRRSEVP3Vbv-CU04VQsnqSHbNasZwLXjzFmDKVV6JQR9mLGLeU8rKk7Hl2VPCCqbKUx9mfy12A9dSb5PxIfEfgp49-MD0ZnA1-9WX599dvzogbyc6MNgCClsQEPaYAsegj2QU_-ATxIWIxhHANYKl1ODQwY0tg3Mx3kaxMPD1ffcastPlh9sTY5K5c2r_MnnWmj_Dqxp9kl-_Pv519zC--fvh0trzIrShlytuuqTpGS1HztqSAJlohW9ZJJRsFrAZeABPKUN6KrpXAgTUls7VomEKmOMneHuri-79PEJPe-imM2FLzoma8llJW99Ta9KDd2PkUjB1ctHpZMcWxg2BILf5DobWAg_QjdA7PHyW8e5CwAdOnTfT9NI8pPgbzA4jriDFAp3fBDSbsNaN6loBGCehZAnqWAPJvbn41NQO0d_Ttzot_V-StGw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2371278886</pqid></control><display><type>article</type><title>Upregulation of exosomal microRNA‑21 in pancreatic stellate cells promotes pancreatic cancer cell migration and enhances Ras/ERK pathway activity</title><source>Spandidos Publications Journals</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Ma, Qiang ; Wu, Huanwen ; Xiao, Ying ; Liang, Zhiyong ; Liu, Tonghua</creator><creatorcontrib>Ma, Qiang ; Wu, Huanwen ; Xiao, Ying ; Liang, Zhiyong ; Liu, Tonghua</creatorcontrib><description>Pancreatic stellate cells (PSCs) are typically activated in pancreatic ductal adenocarcinoma (PDAC) and release exosomes containing high levels of microRNA‑21 (miR‑21). However, the specific roles of exosomal miR‑21 in regulating the PDAC malignant phenotype remain unknown. The present study aimed to determine the effects of exosomal miR‑21 on the migratory ability of PDAC cells and explore the potential underlying molecular mechanism. Weighted gene correlation network and The Cancer Genome Atlas database analysis revealed that high miR‑21 levels were associated with a poor prognosis in patients with pancreatic adenocarcinoma, and that the Ras/ERK signaling pathway may be a potential target of miR‑21. In vitro, PDAC cells were demonstrated to internalize the PSC-derived exosome, resulting in high miR‑21 levels, which subsequently promoted cell migration, induced epithelial‑to‑mesenchymal transition (EMT) and increased matrix metalloproteinase‑2/9 activity. In addition, exosomal miR‑21 increased the levels of ERK1/2 and Akt phosphorylation in PDAC cells. Collectively, these results suggested that PSC‑derived exosomal miR‑21 may promote PDAC cell migration and EMT and enhance Ras/ERK signaling activity. Thus, miR‑21 may be a potential cause of poor prognosis in patients with pancreatic cancer and a new treatment target.</description><identifier>ISSN: 1019-6439</identifier><identifier>EISSN: 1791-2423</identifier><identifier>DOI: 10.3892/ijo.2020.4986</identifier><identifier>PMID: 32319558</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Adenocarcinoma ; Cancer genetics ; Cancer metastasis ; Cell adhesion & migration ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Development and progression ; Electric wire and cable industry ; Epithelial-Mesenchymal Transition ; Exosomes - genetics ; Exosomes - metabolism ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genes ; Genetic aspects ; Genomes ; Genomics ; Humans ; MAP Kinase Signaling System ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Microscopy ; Pancreatic cancer ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Pancreatic Stellate Cells - metabolism ; Pancreatic Stellate Cells - pathology ; Penicillin ; Prognosis ; Proto-Oncogene Proteins p21(ras) - metabolism ; Scientific equipment industry ; Signal Transduction ; Software ; Stem cells ; Up-Regulation ; Wound healing</subject><ispartof>International journal of oncology, 2020-04, Vol.56 (4), p.1025-1033</ispartof><rights>COPYRIGHT 2020 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2020</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-dfb6f105472d50e0e04d48d1f898b9e17e23e149a02d4fd8e2e1b51c74b198983</citedby><cites>FETCH-LOGICAL-c458t-dfb6f105472d50e0e04d48d1f898b9e17e23e149a02d4fd8e2e1b51c74b198983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32319558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Qiang</creatorcontrib><creatorcontrib>Wu, Huanwen</creatorcontrib><creatorcontrib>Xiao, Ying</creatorcontrib><creatorcontrib>Liang, Zhiyong</creatorcontrib><creatorcontrib>Liu, Tonghua</creatorcontrib><title>Upregulation of exosomal microRNA‑21 in pancreatic stellate cells promotes pancreatic cancer cell migration and enhances Ras/ERK pathway activity</title><title>International journal of oncology</title><addtitle>Int J Oncol</addtitle><description>Pancreatic stellate cells (PSCs) are typically activated in pancreatic ductal adenocarcinoma (PDAC) and release exosomes containing high levels of microRNA‑21 (miR‑21). However, the specific roles of exosomal miR‑21 in regulating the PDAC malignant phenotype remain unknown. The present study aimed to determine the effects of exosomal miR‑21 on the migratory ability of PDAC cells and explore the potential underlying molecular mechanism. Weighted gene correlation network and The Cancer Genome Atlas database analysis revealed that high miR‑21 levels were associated with a poor prognosis in patients with pancreatic adenocarcinoma, and that the Ras/ERK signaling pathway may be a potential target of miR‑21. In vitro, PDAC cells were demonstrated to internalize the PSC-derived exosome, resulting in high miR‑21 levels, which subsequently promoted cell migration, induced epithelial‑to‑mesenchymal transition (EMT) and increased matrix metalloproteinase‑2/9 activity. In addition, exosomal miR‑21 increased the levels of ERK1/2 and Akt phosphorylation in PDAC cells. Collectively, these results suggested that PSC‑derived exosomal miR‑21 may promote PDAC cell migration and EMT and enhance Ras/ERK signaling activity. Thus, miR‑21 may be a potential cause of poor prognosis in patients with pancreatic cancer and a new treatment target.</description><subject>Adenocarcinoma</subject><subject>Cancer genetics</subject><subject>Cancer metastasis</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Development and progression</subject><subject>Electric wire and cable industry</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Exosomes - genetics</subject><subject>Exosomes - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Humans</subject><subject>MAP Kinase Signaling System</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Microscopy</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatic Stellate Cells - metabolism</subject><subject>Pancreatic Stellate Cells - pathology</subject><subject>Penicillin</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins p21(ras) - metabolism</subject><subject>Scientific equipment industry</subject><subject>Signal Transduction</subject><subject>Software</subject><subject>Stem cells</subject><subject>Up-Regulation</subject><subject>Wound healing</subject><issn>1019-6439</issn><issn>1791-2423</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptks1u1DAQxyMEoqVw5IosIXHL1nacxD6uqvIhKpBW9Gw5zmTXqyRebKewN14B8YY8CZNuPyU0hxnZv5mxZ_5Z9prRRSEVP3Vbv-CU04VQsnqSHbNasZwLXjzFmDKVV6JQR9mLGLeU8rKk7Hl2VPCCqbKUx9mfy12A9dSb5PxIfEfgp49-MD0ZnA1-9WX599dvzogbyc6MNgCClsQEPaYAsegj2QU_-ATxIWIxhHANYKl1ODQwY0tg3Mx3kaxMPD1ffcastPlh9sTY5K5c2r_MnnWmj_Dqxp9kl-_Pv519zC--fvh0trzIrShlytuuqTpGS1HztqSAJlohW9ZJJRsFrAZeABPKUN6KrpXAgTUls7VomEKmOMneHuri-79PEJPe-imM2FLzoma8llJW99Ta9KDd2PkUjB1ctHpZMcWxg2BILf5DobWAg_QjdA7PHyW8e5CwAdOnTfT9NI8pPgbzA4jriDFAp3fBDSbsNaN6loBGCehZAnqWAPJvbn41NQO0d_Ttzot_V-StGw</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Ma, Qiang</creator><creator>Wu, Huanwen</creator><creator>Xiao, Ying</creator><creator>Liang, Zhiyong</creator><creator>Liu, Tonghua</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20200401</creationdate><title>Upregulation of exosomal microRNA‑21 in pancreatic stellate cells promotes pancreatic cancer cell migration and enhances Ras/ERK pathway activity</title><author>Ma, Qiang ; Wu, Huanwen ; Xiao, Ying ; Liang, Zhiyong ; Liu, Tonghua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-dfb6f105472d50e0e04d48d1f898b9e17e23e149a02d4fd8e2e1b51c74b198983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenocarcinoma</topic><topic>Cancer genetics</topic><topic>Cancer metastasis</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Development and progression</topic><topic>Electric wire and cable industry</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Exosomes - genetics</topic><topic>Exosomes - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Humans</topic><topic>MAP Kinase Signaling System</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Microscopy</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Pancreatic Stellate Cells - metabolism</topic><topic>Pancreatic Stellate Cells - pathology</topic><topic>Penicillin</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins p21(ras) - metabolism</topic><topic>Scientific equipment industry</topic><topic>Signal Transduction</topic><topic>Software</topic><topic>Stem cells</topic><topic>Up-Regulation</topic><topic>Wound healing</topic><toplevel>online_resources</toplevel><creatorcontrib>Ma, Qiang</creatorcontrib><creatorcontrib>Wu, Huanwen</creatorcontrib><creatorcontrib>Xiao, Ying</creatorcontrib><creatorcontrib>Liang, Zhiyong</creatorcontrib><creatorcontrib>Liu, Tonghua</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>International journal of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Qiang</au><au>Wu, Huanwen</au><au>Xiao, Ying</au><au>Liang, Zhiyong</au><au>Liu, Tonghua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of exosomal microRNA‑21 in pancreatic stellate cells promotes pancreatic cancer cell migration and enhances Ras/ERK pathway activity</atitle><jtitle>International journal of oncology</jtitle><addtitle>Int J Oncol</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>56</volume><issue>4</issue><spage>1025</spage><epage>1033</epage><pages>1025-1033</pages><issn>1019-6439</issn><eissn>1791-2423</eissn><abstract>Pancreatic stellate cells (PSCs) are typically activated in pancreatic ductal adenocarcinoma (PDAC) and release exosomes containing high levels of microRNA‑21 (miR‑21). However, the specific roles of exosomal miR‑21 in regulating the PDAC malignant phenotype remain unknown. The present study aimed to determine the effects of exosomal miR‑21 on the migratory ability of PDAC cells and explore the potential underlying molecular mechanism. Weighted gene correlation network and The Cancer Genome Atlas database analysis revealed that high miR‑21 levels were associated with a poor prognosis in patients with pancreatic adenocarcinoma, and that the Ras/ERK signaling pathway may be a potential target of miR‑21. In vitro, PDAC cells were demonstrated to internalize the PSC-derived exosome, resulting in high miR‑21 levels, which subsequently promoted cell migration, induced epithelial‑to‑mesenchymal transition (EMT) and increased matrix metalloproteinase‑2/9 activity. In addition, exosomal miR‑21 increased the levels of ERK1/2 and Akt phosphorylation in PDAC cells. Collectively, these results suggested that PSC‑derived exosomal miR‑21 may promote PDAC cell migration and EMT and enhance Ras/ERK signaling activity. Thus, miR‑21 may be a potential cause of poor prognosis in patients with pancreatic cancer and a new treatment target.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>32319558</pmid><doi>10.3892/ijo.2020.4986</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1019-6439 |
| ispartof | International journal of oncology, 2020-04, Vol.56 (4), p.1025-1033 |
| issn | 1019-6439 1791-2423 |
| language | eng |
| recordid | cdi_proquest_journals_2371278886 |
| source | Spandidos Publications Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma Cancer genetics Cancer metastasis Cell adhesion & migration Cell Line, Tumor Cell Movement Cell Proliferation Development and progression Electric wire and cable industry Epithelial-Mesenchymal Transition Exosomes - genetics Exosomes - metabolism Gene expression Gene Expression Regulation, Neoplastic Genes Genetic aspects Genomes Genomics Humans MAP Kinase Signaling System Metastasis MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism Microscopy Pancreatic cancer Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Pancreatic Stellate Cells - metabolism Pancreatic Stellate Cells - pathology Penicillin Prognosis Proto-Oncogene Proteins p21(ras) - metabolism Scientific equipment industry Signal Transduction Software Stem cells Up-Regulation Wound healing |
| title | Upregulation of exosomal microRNA‑21 in pancreatic stellate cells promotes pancreatic cancer cell migration and enhances Ras/ERK pathway activity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T16%3A00%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Upregulation%20of%20exosomal%20microRNA%E2%80%9121%20in%20pancreatic%20stellate%20cells%20promotes%20pancreatic%20cancer%20cell%20migration%20and%20enhances%20Ras/ERK%20pathway%20activity&rft.jtitle=International%20journal%20of%20oncology&rft.au=Ma,%20Qiang&rft.date=2020-04-01&rft.volume=56&rft.issue=4&rft.spage=1025&rft.epage=1033&rft.pages=1025-1033&rft.issn=1019-6439&rft.eissn=1791-2423&rft_id=info:doi/10.3892/ijo.2020.4986&rft_dat=%3Cgale_proqu%3EA619214941%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2371278886&rft_id=info:pmid/32319558&rft_galeid=A619214941&rfr_iscdi=true |