Evidence map›Paper›PMID 27534557›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2016

MicroRNA-17 Suppresses TNF-α Signaling by Interfering with TRAF2 and cIAP2 Association in Rheumatoid Arthritis Synovial Fibroblasts.

Nahid Akhtar, Anil Kumar Singh, Salahuddin Ahmed

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. microRNAs as Biomarkers and Therapeutic Targets in Rheumatoid Arthritis.International journal of molecular sciences · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Molecular dynamics of inflammation resolution: therapeutic implications.Frontiers in cell and developmental biology · 2025
    Review
  10. Article
  11. Review
  12. Review
  13. E3 ubiquitin ligase geneFrontiers in immunology · 2024
    Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
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

3 authors at 1 institution in 1 country.

Nahid AkhtarDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA 99210.
Anil Kumar SinghDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA 99210.
Salahuddin AhmedDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA 99210 salah.ahmed@wsu.edu.
Washington State University Spokane · US

Funding

Regulation of IL-6 mediated inflammation and tissue destruction by EGCGR01AR063104 · NIAMS · WASHINGTON STATE UNIVERSITY · PI AHMED, SALAH-UDDIN · 2013 to 2017
$1.7M
NIAMS NIH HHS R01 AR063104
6 · The paper itself

Abstract

TNF-α is a major cytokine implicated in rheumatoid arthritis (RA), and its expression is regulated at the transcriptional and posttranscriptional levels. However, the impact of changes in microRNA expression on posttranslational processes involved in TNF-α signaling networks is not well defined in RA. In this study, we evaluated the effect of miR-17, a member of the miR-17-92 cluster, on the TNF-α signaling pathway in human RA synovial fibroblasts (SFs). We demonstrated that miR-17 expression was significantly low in RA serum, SFs, and synovial tissues, as well as in the serum and joints of adjuvant-induced arthritis rats. RNA-sequencing analysis showed modulation of 664 genes by pre-miR-17 in human RA SFs. Ingenuity pathway analysis of RNA-sequencing data identified the ubiquitin proteasome system in the TNF-α signaling pathway as a primary target of miR-17. Western blot analysis confirmed the reduction in TRAF2, cIAP1, cIAP2, USP2, and PSMD13 expression by miR-17 in TNF-α-stimulated RA SFs. Immunoprecipitation assays showed that miR-17 restoration increased the K48-linked polyubiquitination of TRAF2, cIAP1, and cIAP2 in TNF-α-stimulated RA SFs. Thus, destabilization of TRAF2 by miR-17 reduced the ability of TRAF2 to associate with cIAP2, resulting in the downregulation of TNF-α-induced NF-κBp65, c-Jun, and STAT3 nuclear translocation and the production of IL-6, IL-8, MMP-1, and MMP-13 in human RA SFs. In conclusion, this study provides evidence for the role of miR-17 as a negative regulator of TNF-α signaling by modulating the protein ubiquitin processes in RA SFs.

Indexed as

Arthritis, RheumatoidBaculoviral IAP Repeat-Containing 3 ProteinCells, CulturedCytokinesFibroblastsHumansInhibitor of Apoptosis ProteinsMAP Kinase Signaling SystemMatrix Metalloproteinase 1MicroRNAsNF-kappa BSignal TransductionSTAT3 Transcription FactorSynovial MembraneTNF Receptor-Associated Factor 2Tumor Necrosis Factor-alphaBaculoviral IAP Repeat-Containing 3 ProteinBIRC3 protein, humanCytokinesInhibitor of Apoptosis ProteinsMatrix Metalloproteinase 1MicroRNAsMIRN17 microRNA, humanNF-kappa BSTAT3 protein, humanSTAT3 Transcription FactorTNF Receptor-Associated Factor 2Tumor Necrosis Factor-alphaUbiquitinUbiquitin-Protein Ligases

Identifiers

PMID27534557
PMCPMC5010933
OpenAlexW2514090592

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.