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The long noncoding ...
The long noncoding RNA TUNAR modulates Wnt signaling and regulates human β-cell proliferation
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Zhou, A. X. (author)
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- Mondal, Tanmoy, 1981 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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Tabish, A. M. (author)
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Abadpour, S. (author)
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Ericson, E. (author)
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Smith, D. M. (author)
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- Knöll, R. (author)
- Karolinska Institutet
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Scholz, H. (author)
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- Kanduri, Chandrasekhar, 1967 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Tyrberg, Björn (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Althage, M. (author)
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(creator_code:org_t)
- American Physiological Society, 2021
- 2021
- English.
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 320:4
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Abstract
Subject headings
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- Many long noncoding RNAs (lncRNAs) are enriched in pancreatic islets and several lncRNAs are linked to type 2 diabetes (T2D). Although they have emerged as potential players in β-cell biology and T2D, little is known about their functions and mechanisms in human β-cells. We identified an islet-enriched lncRNA, TUNAR (TCL1 upstream neural differentiation-associated RNA), which was upregulated in β-cells of patients with T2D and promoted human β-cell proliferation via fine-tuning of the Wnt pathway. TUNAR was upregulated following Wnt agonism by a glycogen synthase kinase-3 (GSK3) inhibitor in human β-cells. Reciprocally, TUNAR repressed a Wnt antagonist Dickkopf-related protein 3 (DKK3) and stimulated Wnt pathway signaling. DKK3 was aberrantly expressed in β-cells of patients with T2D and displayed a synchronized regulatory pattern with TUNAR at the single cell level. Mechanistically, DKK3 expression was suppressed by the repressive histone modifier enhancer of zeste homolog 2 (EZH2). TUNAR interacted with EZH2 in β-cells and facilitated EZH2-mediated suppression of DKK3. These findings reveal a novel cell-specific epigenetic mechanism via islet-enriched lncRNA that fine-tunes the Wnt pathway and subsequently human β-cell proliferation.NEW & NOTEWORTHY The discovery that long noncoding RNA TUNAR regulates β-cell proliferation may be important in designing new treatments for diabetes.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- DKK3
- long noncoding RNA
- pancreatic β-cell
- TUNAR
- type 2 diabetes
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Zhou, A. X.
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Mondal, Tanmoy, ...
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Tabish, A. M.
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Abadpour, S.
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Ericson, E.
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Smith, D. M.
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show more...
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Knöll, R.
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Scholz, H.
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Kanduri, Chandra ...
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Tyrberg, Björn
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Althage, M.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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American journal ...
- By the university
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University of Gothenburg
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Karolinska Institutet