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Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma

Enokido, Takayoshi (author)
Graduate School of Medicine, University of Tokyo,Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
Horie, Masafumi (author)
Kanazawa Univ, Grad Sch Med Sci, Dept Mol & Cellular Pathol, Kanazawa, Japan.
Yoshino, Seiko (author)
Nagoya University,Nagoya Univ, Ctr Neurol Dis & Canc, Grad Sch Med, Div Mol Oncol, Nagoya, Japan.
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Suzuki, Hiroshi I. (author)
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.
Matsuki, Rei (author)
Graduate School of Medicine, University of Tokyo,Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
Brunnstrom, Hans (author)
Lund 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.
Micke, Patrick (author)
Uppsala universitet,Uppsala University,Cancerimmunterapi
Nagase, Takahide (author)
Graduate School of Medicine, University of Tokyo,Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
Saito, Akira (author)
Graduate School of Medicine, University of Tokyo,Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
Miyashita, Naoya (author)
Duke 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.
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Graduate School of Medicine, University of Tokyo Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan (creator_code:org_t)
American Association For Cancer Research (AACR), 2024
2024
English 12 s.
In: Molecular Cancer Research. - : American Association For Cancer Research (AACR). - 1541-7786 .- 1557-3125. ; 22:1, s. 29-40
Related links:
http://dx.doi.org/10...
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https://lup.lub.lu.s...
https://doi.org/10.1...
https://urn.kb.se/re...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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