Evidence map›Paper›PMID 31156645›Full record

ArticleFrontiers in immunology2019

OTUD6B-AS1 Might Be a Novel Regulator of Apoptosis in Systemic Sclerosis.

Miki Takata, Elena Pachera, Mojca Frank-Bertoncelj, Anastasiia Kozlova, Astrid Jüngel, Michael L Whitfield, Shervin Assassi, Maurizio Calcagni, Jeska de Vries-Bouwstra, Tom W Huizinga and 3 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 47 citations in OpenAlex.

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  10. Characteristics of mJournal of Cancer · 2023
    Article
  11. Novel role of long non-coding RNAs in autoimmune cutaneous disease.Journal of cell communication and signaling · 2022
    Review
  12. Epigenetic Modifications in the Pathogenesis of Systemic Sclerosis.International journal of general medicine · 2022
    Review
  13. Review
  14. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 3 countries.

Miki TakataDepartment of Rheumatology, Center of Experimental Rheumatology, University Hospital Zürich, Zurich, Switzerland.
Elena PacheraDepartment of Rheumatology, Center of Experimental Rheumatology, University Hospital Zürich, Zurich, Switzerland.
Mojca Frank-BertonceljDepartment of Rheumatology, Center of Experimental Rheumatology, University Hospital Zürich, Zurich, Switzerland.
Anastasiia KozlovaDepartment of Rheumatology, Center of Experimental Rheumatology, University Hospital Zürich, Zurich, Switzerland.
Astrid JüngelDepartment of Rheumatology, Center of Experimental Rheumatology, University Hospital Zürich, Zurich, Switzerland.
Michael L WhitfieldDepartment of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
Shervin AssassiDepartment of Internal Medicine, Division of Rheumatology, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, United States.
Maurizio CalcagniDepartment of Plastic Surgery and Hand Surgery, University Hospital Zürich, Zurich, Switzerland.
Jeska de Vries-BouwstraDepartment of Rheumatology, Leiden University Medical Center, Leiden, Netherlands.
Tom W HuizingaDepartment of Rheumatology, Leiden University Medical Center, Leiden, Netherlands.
Fina KurreemanDepartment of Rheumatology, Leiden University Medical Center, Leiden, Netherlands.
Gabriela KaniaDepartment of Rheumatology, Center of Experimental Rheumatology, University Hospital Zürich, Zurich, Switzerland.
Oliver DistlerDepartment of Rheumatology, Center of Experimental Rheumatology, University Hospital Zürich, Zurich, Switzerland.
University Hospital of Zurich · CHLeiden University Medical Center · NLDartmouth College · USThe University of Texas Health Science Center at Houston · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antisense long non-coding RNAs (AS lncRNAs) have increasingly been recognized as important regulators of gene expression and they have been found to play key roles in several diseases. However, very little is known about the role of AS lncRNAs in fibrotic diseases such as systemic sclerosis (SSc). Our recent screening experiments by RNA sequencing showed that ovarian tumor domain containing 6B antisense RNA1 (OTUD6B-AS1) and its sense gene OTUD6B were significantly downregulated in SSc skin biopsies. Therefore, we aimed to identify key regulators of OTUD6B-AS1 and to analyze the functional relevance of OTUD6B-AS1 in SSc. OTUD6B-AS1 and OTUD6B expression in SSc and healthy control (HC) dermal fibroblasts (Fb) after stimulation with transforming growth factor-β (TGFβ), Interleukin (IL)-4, IL-13, and platelet-derived growth factor (PDGF) was analyzed by qPCR. To identify the functional role of OTUD6B-AS1, dermal Fb or human pulmonary artery smooth muscle cells (HPASMC) were transfected with a locked nucleic acid antisense oligonucleotide (ASO) targeting OTUD6B-AS1. Proliferation was measured by BrdU and real-time proliferation assay. Apoptosis was measured by Caspase 3/7 assay and Western blot for cleaved caspase 3. While no difference was recorded at the basal level between HC and SSc dermal Fb, the expression of OTUD6B-AS1 and OTUD6B was significantly downregulated in both SSc and HC dermal Fb after PDGF stimulation in a time-dependent manner. Only mild and inconsistent effects were observed with TGFβ, IL-4, and IL-13. OTUD6B-AS1 knockdown in Fb and HPASMC did not affect extracellular matrix or pro-fibrotic/proinflammatory cytokine production. However, OTUD6B-AS1 knockdown significantly increased Cyclin D1 expression at the mRNA and protein level. Moreover, silencing of OTUD6B-AS1 significantly reduced proliferation and suppressed apoptosis in both dermal Fb and HPASMC. OTUD6B-AS1 knockdown did not affect OTUD6B expression at the mRNA level and protein level. Our data suggest that OTUD6B-AS1 regulates proliferation and apoptosis via cyclin D1 expression in a sense gene independent manner. This is the first report investigating the function of OTUD6B-AS1. Our data shed light on a novel apoptosis resistance mechanism in Fb and vascular smooth muscle cells that might be relevant for pathogenesis of SSc.

Indexed as

ApoptosisCell ProliferationCells, CulturedCyclin DEndopeptidasesEndoplasmic Reticulum, SmoothFibroblastsGene Expression RegulationGene Knockdown TechniquesHumansMyocytes, Smooth MuscleRNA, AntisenseRNA, Long NoncodingScleroderma, SystemicSkinCyclin DEndopeptidasesOTUD6B protein, humanRNA, AntisenseRNA, Long Noncodingantisense long non-coding RNA (AS lncRNA)apoptosiscyclin D1dermal fibroblastshuman pulmonary artery smooth muscle cellsovarian tumor domain containing 6B-antisense RNA1 (OTUD6B-AS1)proliferationsystemic sclerosis

Identifiers

PMID31156645
PMCPMC6533854
OpenAlexW2946213042

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.