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Article: Dual inhibition of cMET and EGFR by microRNA-338-5p suppresses metastasis of esophageal squamous cell carcinoma

TitleDual inhibition of cMET and EGFR by microRNA-338-5p suppresses metastasis of esophageal squamous cell carcinoma
Authors
Issue Date2021
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2021, v. 42 n. 7, p. 995-1007 How to Cite?
AbstractMicroRNAs, as a group of post-transcriptional regulators, regulate multiple pathological processes including metastasis during tumor development. Here, we demonstrated the metastasis-suppressive function of microRNA (miR)-338-5p in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-338-5p had inhibitory effect on invasive ability of ESCC cells and extracellular matrix degradation, whereas silencing miR-338-5p had opposite effects. Mechanistically, miR-338-5p directly targeted the 3′ untranslated regions of hepatocellular growth factor receptor cMet (cMET) and epidermal growth factor receptor (EGFR). As a result, miR-338-5p inhibited the downstream signaling cascades of cMET and EGFR and repressed cMET- and EGFR-mediated ESCC cell invasion. Re-expression of cMET or EGFR in miR-338-5p overexpressing ESCC cells was sufficient to derepress ESCC cell invasion both in vitro and in vivo. We further showed that such manipulation downregulated the expression and secretion of matrix metalloproteinases 2 and 9, which resulted in impaired extracellular matrix degradation and cell invasion. Most importantly, systemic delivery of miR-338-5p mimic significantly inhibited metastasis of ESCC cells in nude mice. Taken together, our results uncovered a previously unknown mechanism through which miR-338-5p suppresses ESCC invasion and metastasis by regulating cMET/EGFR-matrix metalloproteinase 2/9 axis and highlighted the potential significance of miR-338-5p-based therapy in treating patients with metastatic ESCC.
Persistent Identifierhttp://hdl.handle.net/10722/301239
ISSN
2023 Impact Factor: 3.3
2023 SCImago Journal Rankings: 1.074
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCui, D-
dc.contributor.authorZhu, Y-
dc.contributor.authorYan, D-
dc.contributor.authorLee, NPY-
dc.contributor.authorHan, L-
dc.contributor.authorLaw, SYK-
dc.contributor.authorTsao, GSW-
dc.contributor.authorCheung, ALM-
dc.date.accessioned2021-07-27T08:08:10Z-
dc.date.available2021-07-27T08:08:10Z-
dc.date.issued2021-
dc.identifier.citationCarcinogenesis, 2021, v. 42 n. 7, p. 995-1007-
dc.identifier.issn0143-3334-
dc.identifier.urihttp://hdl.handle.net/10722/301239-
dc.description.abstractMicroRNAs, as a group of post-transcriptional regulators, regulate multiple pathological processes including metastasis during tumor development. Here, we demonstrated the metastasis-suppressive function of microRNA (miR)-338-5p in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-338-5p had inhibitory effect on invasive ability of ESCC cells and extracellular matrix degradation, whereas silencing miR-338-5p had opposite effects. Mechanistically, miR-338-5p directly targeted the 3′ untranslated regions of hepatocellular growth factor receptor cMet (cMET) and epidermal growth factor receptor (EGFR). As a result, miR-338-5p inhibited the downstream signaling cascades of cMET and EGFR and repressed cMET- and EGFR-mediated ESCC cell invasion. Re-expression of cMET or EGFR in miR-338-5p overexpressing ESCC cells was sufficient to derepress ESCC cell invasion both in vitro and in vivo. We further showed that such manipulation downregulated the expression and secretion of matrix metalloproteinases 2 and 9, which resulted in impaired extracellular matrix degradation and cell invasion. Most importantly, systemic delivery of miR-338-5p mimic significantly inhibited metastasis of ESCC cells in nude mice. Taken together, our results uncovered a previously unknown mechanism through which miR-338-5p suppresses ESCC invasion and metastasis by regulating cMET/EGFR-matrix metalloproteinase 2/9 axis and highlighted the potential significance of miR-338-5p-based therapy in treating patients with metastatic ESCC.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/-
dc.relation.ispartofCarcinogenesis-
dc.rightsThis is a pre-copy-editing, author-produced PDF of an article accepted for publication in Carcinogenesis following peer review. The definitive publisher-authenticated version Carcinogenesis, 2021, v. 42 n. 7, p. 995-1007 is available online at: https://academic.oup.com/carcin/article-abstract/42/7/995/6293877?redirectedFrom=fulltext-
dc.titleDual inhibition of cMET and EGFR by microRNA-338-5p suppresses metastasis of esophageal squamous cell carcinoma-
dc.typeArticle-
dc.identifier.emailLee, NPY: nikkilee@hku.hk-
dc.identifier.emailLaw, SYK: slaw@hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailCheung, ALM: lmcheung@hku.hk-
dc.identifier.authorityLee, NPY=rp00263-
dc.identifier.authorityLaw, SYK=rp00437-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityCheung, ALM=rp00332-
dc.description.naturepostprint-
dc.identifier.doi10.1093/carcin/bgab046-
dc.identifier.pmid34089582-
dc.identifier.scopuseid_2-s2.0-85112125745-
dc.identifier.hkuros323692-
dc.identifier.volume42-
dc.identifier.issue7-
dc.identifier.spage995-
dc.identifier.epage1007-
dc.identifier.isiWOS:000733762100010-
dc.publisher.placeUnited Kingdom-

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