Down-regulation of microRNA-142-3p inhibits the aggressive phenotypes of rheumatoid arthritis fibroblast-like synoviocytes through inhibiting nuclear factor-κB signaling
Authors: Tingting Lv
Jianhong Qiang
Xichao Yang
Zhenbiao Wu
Journal: Bioscience reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Inflammation; MicroRNA-142-3p; Nuclear factor-kappa B; Proliferation; Tumor necrosis factor α.
Affiliations: Department of Traditional Chinese Medicine, Yan'An People's Hospital, No. 57, Qilipu Street, Baota District, Yan'an City 716000, Shaanxi Province, China., Department of Rheumatology and Immunology, The Second Affiliated Hospital of The Fourth Military Medical University, No. 569, Xinsi Road, Xi'an City 710038, Shaanxi Province, China., Department of Clinical Immunology, The First Affiliated Hospital of The Fourth Military Medical University, No. 1, Changle East Road, Xi'an City 710032, Shaanxi Province, China., Department of Clinical Immunology, The First Affiliated Hospital of The Fourth Military Medical University, No. 1, Changle East Road, Xi'an City 710032, Shaanxi Province, China .

Abstract:  The present study aimed to investigate the regulatory roles of miR-142-3p on the aggressive phenotypes of rheumatoid arthritis (RA) human fibroblast-like synoviocytes (RA-HFLSs), and reveal the potential mechanisms relating with nuclear factor-κB (NF-κB) signaling. miR-142-3p expression was detected in RA synovial tissues and RA-HFLSs by quantitative real-time PCR (qRT-PCR) and Northern blot analysis. RA-HFLSs were transfected with miR-142-3p inhibitor and/or treated with 10 µg/l tumor necrosis factor α (TNF-α). The viability, colony formation, apoptosis, migration, invasion, and the levels of interleukin (IL)-6, and matrix metalloproteinase 3 (MMP-3) were detected. The mRNA expressions of B-cell lymphoma-2 (Bcl-2), Bax, Bad, IL-6, and MMP-3 were detected by qRT-PCR. Moreover, the expression of Bcl-2, IL-1 receptor-associated kinase 1 (IRAK1), Toll-like receptor 4 (TLR4), NF-κB p65, and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by Western blot. The interaction between IRAK1 and miR-142-3p was identified by dual luciferase reporter gene assay. MiR-142-3p was up-regulated in RA synovial tissues and RA-HFLSs. TNF-α activated the aggressive phenotypes of RA-HFLSs, including enhanced proliferation, migration, invasion, and inflammation, and inhibited apoptosis. miR-142-3p inhibitor significantly decreased the cell viability, the number of cell clones, the migration rate, the number of invasive cells, the contents and expression of IL-6 and MMP-3, and increased the apoptosis rate and the expressions of Bax and Bad, and decreased Bcl-2 expression of TNF-α-treated RA-HFLSs. MiR-142-3p inhibitor significantly reversed TNF-α-induced up-regulation of IRAK1, TLR4, and p-NF-κB p65 in TNF-α-treated RA-HFLSs. Besides, IRAK1 was a target of miR-142-3p. The down-regulation of miR-142-3p inhibited the aggressive phenotypes of RA-HFLSs through inhibiting NF-κB signaling. 

Retracted: No

PubPeer comments:
 Figure 1D and 1E appear to contain a repeated band, represent in two different conditions. Could the authors please post an uncropped original scan? *** ![file] *** ![file] , 
 Figure 4B also has some issues. when one of the images is flipped vertically overlaps can be seen with an adjacent image, however some areas (see yellow) are *not* identical. Very concerning. *** ![file] *** Original 4B ![file] , 
 The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. , 
 Dear editor, Thank you very much for your letter. Can we replace Figure 1 and Figure 4? As the picture is too big, I have sent it by email.Thanks. Best wishes , 
 #2 My attempt to dramatise the problem within Fig 4B. Not just two panels that overlap when one is flipped vertically, but two smaller, circumscribed areas of overlap, involving slightly different vertical horizontal offsets. ![file] I am sure that readers will welcome a corrected version of Fig 4B, without these anomalies, but they may also wonder how the anomalies ever entered the Figure in the first place. , 
 #4 Dr. Yang: Thank you for your reply. To be clear, to make a correction to the manuscript you will need to correspond with the journal editors directly, not the hosts of this post publication review site. If you no longer have the journalu2019s contact information, perhaps try: editorial@portlandpress.com Readers here *would* be interested in seeing the replacement figure, which you can upload elsewhere and share a link to that image here. , 
 Retracted [01 September 2020] .  This retraction follows an Expression of Concern relating to this article previously published by Portland Press. This article is being retracted from Bioscience Reports at the request of the Editor in Chief and the Editorial Board following receipt of a notification from a reader, alerting the Editorial Board to repeated bands in the Western blots of Figures 1D and E, as well as image manipulation in Figure 4B. The authors were contacted regarding the concerns raised and provided a replacement Figures 1D and 4B, however given that the original images in Figure 4B showed signs of manipulation, the Editorial Board stands by the decision to retract. The authors disagree to the retraction. ,