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BARX2/FOXA1/HK2 axis promotes lung adenocarcinoma progression and energy metabolism reprogramming

dc.contributor.authorXie, Kai
dc.contributor.authorFeng, Jian
dc.contributor.authorFan, Dingwei
dc.contributor.authorWang, Shi
dc.contributor.authorLuo, Jing
dc.contributor.authorRen, Zhijian
dc.contributor.authorZheng, Chao
dc.contributor.authorDiao, Yifei
dc.contributor.authorDe Mello, Ramon Andrade
dc.contributor.authorTavolari, Simona
dc.contributor.authorBrandi, Giovanni
dc.contributor.authorRoden, Anja C.
dc.contributor.authorRen, Binhui
dc.contributor.authorShen, Yi
dc.contributor.authorXu, Lin
dc.date.accessioned2022-12-21T14:01:46Z
dc.date.available2022-12-21T14:01:46Z
dc.date.issued2022
dc.description.abstractBackground: Metabolic reprogramming is an emerging cancer feature that has recently drawn special attention since it promotes tumor cell growth and proliferation. However, the mechanism of the Warburg effect is still largely unknown. This research aimed to reveal the effects of BarH-like homeobox 2 (BARX2) in regulating tumor progression and glucose metabolism in lung adenocarcinoma (LUAD).Methods: Expression of BARX2 was measured by quantitative real-time polymerase chain reaction (qRTPCR) in LUAD cell line and tissues, and the tumor-promoting function of BARX2 in LUAD cells was detected in vitro and in vivo xenograft models. The metabolic effects of BARX2 were examined by detecting glucose uptake, the production levels of lactate and pyruvate, and the extracellular acidification rate (ECAR). Chromatin immunoprecipitation (ChIP) assay and luciferase reporter gene assay were used to identify the underlying molecular mechanism of BARX2 regulation of HK2. Further studies showed that transcription factor FOXA1 directly interacts with BARX2 and promotes the transcriptional activity of BARX2.Results: BARX2 was remarkably up-regulated in LUAD tissues and positively linked to advanced clinical stage and poor prognosis. In vitro and in vivo data indicated ectopic expression of BARX2 enhanced cell proliferation and tumorigenesis, whereas BARX2 knockdown suppressed these effects. Metabolic-related experiments showed BARX2 promoted the reprogramming of glucose metabolism. Mechanistically, the BARX2/FOXA1/HK2 axis promoted LUAD progression and energy metabolism reprogramming.Conclusions: In summary, our research first defined BARX2 as a tumor-promoting factor in LUAD andthat it may act as a novel prognostic biomarker and new therapeutic target for the disease.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.21037/tlcr-22-465pt_PT
dc.identifier.issn2218-6751
dc.identifier.urihttp://hdl.handle.net/10400.1/18696
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAME Publishing Companypt_PT
dc.subjectTranscription factorpt_PT
dc.subjectBARX2pt_PT
dc.subjectLung adenocarcinoma (LUAD)pt_PT
dc.subjectGlucose metabolismpt_PT
dc.subjectHK2pt_PT
dc.titleBARX2/FOXA1/HK2 axis promotes lung adenocarcinoma progression and energy metabolism reprogrammingpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1419pt_PT
oaire.citation.issue7pt_PT
oaire.citation.startPage1405pt_PT
oaire.citation.titleTranslational Lung Cancer Researchpt_PT
oaire.citation.volume11pt_PT
person.familyNamede Mello
person.givenNameRamon Andrade
person.identifier.orcid0000-0002-9640-4573
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication53ee625f-c5c3-468b-85bb-4cef5ad36928
relation.isAuthorOfPublication.latestForDiscovery53ee625f-c5c3-468b-85bb-4cef5ad36928

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