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Article: MicroRNA 744-3p promotes MMP-9-mediated metastasis by simultaneously suppressing PDCD4 and PTEN in laryngeal squamous cell carcinoma

TitleMicroRNA 744-3p promotes MMP-9-mediated metastasis by simultaneously suppressing PDCD4 and PTEN in laryngeal squamous cell carcinoma
Authors
KeywordsLaryngeal squamous cell carcinoma
Metastasis
PDCD4
PTEN
MiR-744-3p
Issue Date2016
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2016, v. 7 n. 36, p. 58218-58233 How to Cite?
AbstractMicroRNA controls cancer invasion by governing the expression of gene regulating migration and invasion. Here, we reported a novel regulatory pathway controlled by miR-744-3p, which enhanced expression of matrix metallopeptidase 9 (MMP-9) in laryngeal squamous cell carcinoma (LSCC). We profiled the differential micoRNA expression pattern in LSCC cell lines and normal epithelial cultures derived from the head and neck mucosa using microRNA microarray. MiR-7-1-3p, miR-196a/b and miR-744-3p were expressed differentially in the LSCC cell lines. Subsequent validation using real-time PCR revealed that high miR-744-3p level was positively correlated with regional lymph node metastasis of LSCC. Real-time cellular kinetic analysis showed that suppressing miR-744-3p could inhibit migration and invasion of LSCC cell lines and reduce the number of lung metastatic nodules in nude mice modules. In silico analysis revealed that miR-744-3p targeted 2 distinct signaling cascades which eventually upregulated MMP-9 expression in LSCC. First, miR-744-3p could suppress programmed cell death 4 (PDCD4), a direct suppressor of NF-κB (p65). PDCD4 could also prevent AKT activation and suppress MMP-9 expression. Further, suppressing miR-744-3p expression could restore phosphatase and tensin homolog (PTEN) expression. PTEN could inhibit AKT activation and inhibit MMP-9 expression in LSCC cells. The results revealed that suppressing miR-744-3p was effective to inhibit LSCC metastasis by inactivating AKT/mTOR and NF-κB (p65) signaling cascade. Targeting miR-744-3p could be a valuable therapeutic intervention to suppress the aggressiveness of LSCC.
Persistent Identifierhttp://hdl.handle.net/10722/243831
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, Z-
dc.contributor.authorGao, W-
dc.contributor.authorLei, WB-
dc.contributor.authorZhao, J-
dc.contributor.authorChan, YW-
dc.contributor.authorWei, WI-
dc.contributor.authorHo, WK-
dc.contributor.authorWong, TS-
dc.date.accessioned2017-08-25T03:00:05Z-
dc.date.available2017-08-25T03:00:05Z-
dc.date.issued2016-
dc.identifier.citationOncotarget, 2016, v. 7 n. 36, p. 58218-58233-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/243831-
dc.description.abstractMicroRNA controls cancer invasion by governing the expression of gene regulating migration and invasion. Here, we reported a novel regulatory pathway controlled by miR-744-3p, which enhanced expression of matrix metallopeptidase 9 (MMP-9) in laryngeal squamous cell carcinoma (LSCC). We profiled the differential micoRNA expression pattern in LSCC cell lines and normal epithelial cultures derived from the head and neck mucosa using microRNA microarray. MiR-7-1-3p, miR-196a/b and miR-744-3p were expressed differentially in the LSCC cell lines. Subsequent validation using real-time PCR revealed that high miR-744-3p level was positively correlated with regional lymph node metastasis of LSCC. Real-time cellular kinetic analysis showed that suppressing miR-744-3p could inhibit migration and invasion of LSCC cell lines and reduce the number of lung metastatic nodules in nude mice modules. In silico analysis revealed that miR-744-3p targeted 2 distinct signaling cascades which eventually upregulated MMP-9 expression in LSCC. First, miR-744-3p could suppress programmed cell death 4 (PDCD4), a direct suppressor of NF-κB (p65). PDCD4 could also prevent AKT activation and suppress MMP-9 expression. Further, suppressing miR-744-3p expression could restore phosphatase and tensin homolog (PTEN) expression. PTEN could inhibit AKT activation and inhibit MMP-9 expression in LSCC cells. The results revealed that suppressing miR-744-3p was effective to inhibit LSCC metastasis by inactivating AKT/mTOR and NF-κB (p65) signaling cascade. Targeting miR-744-3p could be a valuable therapeutic intervention to suppress the aggressiveness of LSCC.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectLaryngeal squamous cell carcinoma-
dc.subjectMetastasis-
dc.subjectPDCD4-
dc.subjectPTEN-
dc.subjectMiR-744-3p-
dc.titleMicroRNA 744-3p promotes MMP-9-mediated metastasis by simultaneously suppressing PDCD4 and PTEN in laryngeal squamous cell carcinoma-
dc.typeArticle-
dc.identifier.emailLi, Z: zenghong@hku.hk-
dc.identifier.emailGao, W: weigao@graduate.hku.hk-
dc.identifier.emailZhao, J: zhaoj39@hku.hk-
dc.identifier.emailChan, YW: jywchan1@hku.hk-
dc.identifier.emailWei, WI: hrmswwi@hku.hk-
dc.identifier.emailHo, WK: wkho@hkucc.hku.hk-
dc.identifier.emailWong, TS: thiansze@graduate.hku.hk-
dc.identifier.authorityGao, W=rp02222-
dc.identifier.authorityChan, YW=rp01314-
dc.identifier.authorityWei, WI=rp00323-
dc.identifier.authorityWong, TS=rp00478-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/oncotarget.11280-
dc.identifier.pmcidPMC5295426-
dc.identifier.scopuseid_2-s2.0-84988429337-
dc.identifier.hkuros274335-
dc.identifier.volume7-
dc.identifier.issue36-
dc.identifier.spage58218-
dc.identifier.epage58233-
dc.identifier.isiWOS:000387153200062-
dc.publisher.placeUnited States-

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