Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41389-018-0050-x
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dc.titleDysregulation of the MiR-449b target TGFBI alters the TGF? pathway to induce cisplatin resistance in nasopharyngeal carcinoma
dc.contributor.authorBissey, P.-A
dc.contributor.authorLaw, J.H
dc.contributor.authorBruce, J.P
dc.contributor.authorShi, W
dc.contributor.authorRenoult, A
dc.contributor.authorChua, M.L.K
dc.contributor.authorYip, K.W
dc.contributor.authorLiu, F.-F
dc.date.accessioned2020-10-30T02:07:57Z
dc.date.available2020-10-30T02:07:57Z
dc.date.issued2018
dc.identifier.citationBissey, P.-A, Law, J.H, Bruce, J.P, Shi, W, Renoult, A, Chua, M.L.K, Yip, K.W, Liu, F.-F (2018). Dysregulation of the MiR-449b target TGFBI alters the TGF? pathway to induce cisplatin resistance in nasopharyngeal carcinoma. Oncogenesis 7 (5) : 40. ScholarBank@NUS Repository. https://doi.org/10.1038/s41389-018-0050-x
dc.identifier.issn21579024
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/182083
dc.description.abstractDespite the improvement in locoregional control of nasopharyngeal carcinoma (NPC), distant metastasis (DM), and chemoresistance persist as major causes of mortality. This study identified a novel role for miR-449b, an overexpressed gene in a validated four-miRNA signature for NPC DM, leading to chemoresistance via the direct targeting of transforming growth factor beta-induced (TGFBI). In vitro shRNA-mediated downregulation of TGFBI induced phosphorylation of PTEN and AKT, increasing cisplatin resistance. Conversely, the overexpression of TGFBI sensitized the NPC cells to cisplatin. In NPC patients treated with concurrent chemoradiotherapy (CRT), the overall survival (OS) was significantly inversely correlated with miR-449b, and directly correlated with both TGFBI mRNA and protein expression, as assessed by RNA sequencing and immunohistochemistry (IHC). Mechanistically, co-immunoprecipitation demonstrated that TGFBI competes with pro-TGF?1 for integrin receptor binding. Decreased TGFBI led to increased pro-TGF?1 activation and TGF?1 canonical/noncanonical pathway-induced cisplatin resistance. Thus, overexpression of miR-449b decreases TGFBI, thereby altering the balance between TGFBI and pro-TGF?1, revealing a novel mechanism of chemoresistance in NPC. © 2018 The Author(s).
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectbeta actin
dc.subjectcaspase 3
dc.subjectcisplatin
dc.subjectfizzy related protein
dc.subjectintegrin receptor
dc.subjectmessenger RNA
dc.subjectmicroRNA
dc.subjectmicroRNA 449b
dc.subjectphosphatidylinositol 3,4,5 trisphosphate 3 phosphatase
dc.subjectprotein kinase B
dc.subjectshort hairpin RNA
dc.subjectSmad2 protein
dc.subjecttranscription factor ZEB1
dc.subjecttransforming growth factor beta
dc.subjecttransforming growth factor beta induced
dc.subjecttransforming growth factor beta1
dc.subjectunclassified drug
dc.subjectvimentin
dc.subjectapoptosis
dc.subjectArticle
dc.subjectcancer resistance
dc.subjectchemoradiotherapy
dc.subjectdown regulation
dc.subjectenzyme activation
dc.subjectenzyme activity
dc.subjectenzyme phosphorylation
dc.subjecthuman
dc.subjecthuman cell
dc.subjectimmunohistochemistry
dc.subjectimmunoprecipitation
dc.subjectin vitro study
dc.subjectmetastasis
dc.subjectnasopharynx carcinoma
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectprotein phosphorylation
dc.subjectRNA sequence
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1038/s41389-018-0050-x
dc.description.sourcetitleOncogenesis
dc.description.volume7
dc.description.issue5
dc.description.page40
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