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Distinct microRNA S...
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Enokido, TakayoshiGraduate School of Medicine, University of Tokyo,Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
(författare)
Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
- Artikel/kapitelEngelska2024
Förlag, utgivningsår, omfång ...
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American Association For Cancer Research (AACR),2024
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12 s.
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:656a624a-7f1e-471b-8198-b8cad8b9f83f
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https://lup.lub.lu.se/record/656a624a-7f1e-471b-8198-b8cad8b9f83fURI
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https://doi.org/10.1158/1541-7786.MCR-23-0229DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-524635URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Achaete-scute family bHLH transcription factor 1 (ASCL1) is a master transcription factor involved in neuroendocrine differentiation. ASCL1 is expressed in approximately 10% of lung adenocarcinomas (LUAD) and exerts tumor-promoting effects. Here, we explored miRNA profiles in ASCL1-positive LUADs and identified several miRNAs closely associated with ASCL1 expression, including miR-375, miR-95–3p/miR-95–5p, miR-124–3p, and members of the miR-17~92 family. Similar to small cell lung cancer, Yes1 associated transcriptional regulator (YAP1), a representative miR-375 target gene, was suppressed in ASCL1-positive LUADs. ASCL1 knockdown followed by miRNA profiling in a cell culture model further revealed that ASCL1 positively regulates miR-124–3p and members of the miR-17~92 family. Integrative transcriptomic analyses identified ZFP36 ring finger protein like 1 (ZFP36L1) as a target gene of miR-124–3p, and IHC studies demonstrated that ASCL1-positive LUADs are associated with low ZFP36L1 protein levels. Cell culture studies showed that ectopic ZFP36L1 expression inhibits cell proliferation, survival, and cell-cycle progression. Moreover, ZFP36L1 negatively regulated several genes including E2F transcription factor 1 (E2F1) and snail family transcriptional repressor 1 (SNAI1). In conclusion, our study revealed that suppression of ZFP36L1 via ASCL1-regulated miR-124–3p could modulate gene expression, providing evidence that ASCL1-mediated regulation of miRNAs shapes molecular features of ASCL1-positive LUADs.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Horie, MasafumiKanazawa Univ, Grad Sch Med Sci, Dept Mol & Cellular Pathol, Kanazawa, Japan.
(författare)
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Yoshino, SeikoNagoya University,Nagoya Univ, Ctr Neurol Dis & Canc, Grad Sch Med, Div Mol Oncol, Nagoya, Japan.
(författare)
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Suzuki, Hiroshi I.Nagoya University,Nagoya Univ, Ctr Neurol Dis & Canc, Grad Sch Med, Div Mol Oncol, Nagoya, Japan.;Nagoya Univ, Inst Glyco Core Res iGCORE, Nagoya, Japan.;Nagoya Univ, Ctr One Med Innovat Translat Res COMIT, Nagoya, Japan.
(författare)
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Matsuki, ReiGraduate School of Medicine, University of Tokyo,Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
(författare)
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Brunnstrom, HansLund University,Lunds universitet,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Region Skåne,Lund Univ, Dept Clin Sci Lund, Lab Med Reg Skane, Pathol, Lund, Sweden.(Swepub:lu)med-hsb
(författare)
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Micke, PatrickUppsala universitet,Uppsala University,Cancerimmunterapi(Swepub:uu)patmi676
(författare)
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Nagase, TakahideGraduate School of Medicine, University of Tokyo,Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
(författare)
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Saito, AkiraGraduate School of Medicine, University of Tokyo,Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
(författare)
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Miyashita, NaoyaDuke University,Graduate School of Medicine, University of Tokyo,Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.;Duke Univ, Sch Med, Dept Cell Biol, Durham, NC 27710 USA.
(författare)
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Graduate School of Medicine, University of TokyoUniv Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Molecular Cancer Research: American Association For Cancer Research (AACR)22:1, s. 29-401541-77861557-3125
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Enokido, Takayos ...
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Horie, Masafumi
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Yoshino, Seiko
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Suzuki, Hiroshi ...
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Matsuki, Rei
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Brunnstrom, Hans
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visa fler...
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Micke, Patrick
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Nagase, Takahide
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Saito, Akira
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Miyashita, Naoya
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