miR‚Ä?52 inhibits rheumatoid arthritis synovial fibroblast proliferation and induces apoptosis by targeting ADAM10
Authors: Juan Du
Dan Fei
Jie Xing
Honghua Lu
Jialong Guo
Jinxiang Liu
Journal: International Journal of Molecular Medicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: miR-152; rheumatoid arthritis; functional role; molecular mechanisms; serum
Affiliations: Department of Rheumatology and Immunology, The China‚ÄëJapan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China., Ultrasonographic Department, The China‚ÄëJapan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China., Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Abstract:  miR‚Ä?52 has been reported to be downregulated in rheumatoid arthritis (RA). However, the functional significance and molecular mechanisms underlying the role of miR‚Ä?52 in RA remain largely unknown. The present study aimed to explore the functional role and the underlying mechanisms of miR‚Ä?52 in RA. The expression of miR‚Ä?52 in serum, synovial tissues, and fibroblast‚Äëlike synoviocytes (FLS) from patients with RA and healthy controls was detected by reverse transcription‚Äëquantitative polymerase chain reaction (RT‚ÄëqPCR). Cell proliferation, cell cycle phase distribution and apoptosis of FLS were measured by Cell Counting Kit‚Ä? and flow cytometry assays. The effects of miR‚Ä?52 on the production of pro‚Äëinflammatory cytokines, including tumor necrosis factor (TNF)‚ÄëŒ? interleukin (IL)‚Ä?Œ≤, IL‚Ä? and IL‚Ä?, were examined by ELISA. The target gene of miR‚Ä?52 was discovered by miRNA‚Äëtarget prediction bioinformatics analysis, and confirmed by dual‚Äëluciferase reporter assay, RT‚ÄëqPCR and western blotting. Spearman's correlation analysis was performed to assess the relationship between miR‚Ä?52 expression and a disintegrin and metalloproteinase domain‚Äëcontaining protein 10 (ADAM10). The results demonstrated that miR‚Ä?52 expression levels were significantly decreased in RA serum, synovial tissues and RA‚ÄëFLS compared with healthy controls. Overexpression of miR‚Ä?52 significantly inhibited cell proliferation, promoted cell apoptosis, and decreased TNF‚ÄëŒ? IL‚Ä?Œ≤, IL‚Ä? and IL‚Ä? production in RA‚ÄëFLS cells. Additionally, ADAM10 was demonstrated to be a target of miR‚Ä?52, and expression of the two genes was significantly negatively correlated. Of note, restoration of ADAM10 expression partially reversed the effects of miR‚Ä?52 on cell proliferation and apoptosis in RA‚ÄëFLS. Thus, miR‚Ä?52 may serve as a potential target for therapeutic intervention in RA. 

Retracted: Yes

PubPeer comments:
 *[left]* Fig 2D.  ...apoptosis were determined in RA-FLS post-transfection . *[right]* Fig 2D from [Lin et al (2017)] .  Cell apoptosis were determined in TPC-1 and SW1736 cells transfected with miR-NC or miR-217 mimic .  Different studies, no authors in common, shared panels. , 
 Retracted [14 July 2021] .  Following the publication of this paper, the authors alerted the Editorial Office to the fact that a reader had informed them that miRu2011152 overexpression did not affect cell apoptosis and cell cycle. The authors subsequently confirmed that they were unable to obtain consistent results from these experiments. Furthermore, an independent investigation of this paper revealed that the cell apoptotic data shown in Fig. 2D were strikingly similar to those that had appeared in an article published previously with different authors, although one of the institutions was held in common. The authors have requested that the above article be retracted from the publication, and the Editor agrees with this course of action. The Editor apologizes to the readership for any inconvenience caused.  An independent investigation presumably means  we read a post at Pubpeer . ,