Up-regulated microRNA-411 or declined RIPK1 inhibits proliferation and promotes apoptosis of synoviocytes in rheumatoid arthritis mice via decreased NF-κB pathway
Authors: Kaizhe Chen
Huachen Yu
Lianfu Deng
Xiaoyun Pan
Xinghe Xue
Daosen Chen
Yu Zhang
Yijiang Huang
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RIPK1; Rheumatoid arthritis; microrna-411.
Affiliations: Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China., Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, 325000, Zhejiang Province, China., Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai jiaotong University School of Medicine, Shanghai 200003, China.

Abstract:  Rheumatoid arthritis (RA) is a chronic and inflammatory synovitis systemic disease. Due to the unknown pathogenesis, this study was to investigate the effect of microRNA (miR)-411 on apoptosis and joint function of synoviocytes in RA mice via RIPK1-mediated NF-κB signaling pathway. The collagen-induced arthritis model mice were induced via collagen type II and Freund's adjuvant. The mice were injected with miR-411 mimics, si-RIPK1 or miR-411 mimics + oe-RIPK1 to figure out their roles in cell apoptosis and inflammation of synovial tissues. Synoviocytes were grouped as in animal experiments. Proliferation and apoptosis of synoviocytes were detected upon treatment with overexpressed miR-411 and silenced RIPK1. The expression of miR-411, RIPK1 and NF-κB in synovial tissues and synoviocytes of RA mice was detected by RT-qPCR and Western blot analysis. Poorly expressed miR-411, and highly expressed NF-κB and RIPK1 existed in synovial tissue and synoviocytes of RA. Additionally, it was found that si-RIPK1 decreased NF-κB expression, and miR-411 mimics decreased both RIPK1 and NF-κB. MiR-411 had a targeted relationship with RIPK1. si-RIPK1 or miR-411 mimics promoted cell apoptosis and strained inflammation in synovial tissues of mice with RA. Overexpressed miR-411 or silencing RIPK1 inhibited the proliferation and promoted apoptosis of synoviocytes of RA mice. Up-regulation of miR-411 or down-regulation of RIPK1 had a certain inhibitory effect on RA. This study suggests that up-regulated miR-411 or down-regulated RIPK1 promoted apoptosis and inhibited proliferation of synoviocytes of RA mice, which may be related to the inhibition of NF-κB activation. 

Retracted: Yes

PubPeer comments:
 Figure 1BC * Marked in orange: The Tti1 blot in Figure 1B looks very similar to the Tel2 blot in Figure 1C. Could the authors please check? ![file] , 
 More identical blots used as results from separate experiments. Please clarify. ![file] , 
 ![file] , 
 Dear Dr. Bik and Pubpeer commenters, Thank you for your comment on our paper. This is Feng Rao, first author of the paper. I am writing in cosultation with Dr. Snyder.u3000 We have carefully checked the indicated duplication of images and confirmed that, while there is no duplication between the mTOR blots in Fig 3G, the Tel2 after GST pulldown blot in Fig 1C was inadvertently duplicated from the Tti1 after GST pulldown blot in Fig 1B, and the Tti1 input blot in Fig 1D was an inadvertent duplication of the Tti1 blot in Fig 3F. This mistake likely arises during figure assembly, whereby, due to the similar figure labeling framework between Fig1B and 1C, and between Fig 1D and 3F, a copy-paste was conducted to retain the labeling framework, but subsequent blot replacement was incomplete. Fortunately, we found the original images for the correct Tel2 and Tti1 blot in Fig 1C and 1D, which were dated between 2011-2013, the period when the data was acquired. We are now working with the journal to issue a correction to fix the problem. Thanks again for pointing out this error. Feng Rao Sol Snyder ![file] ![file] ![file] , 
 Why did the author not addressing the #2 and #3 comments in the Erratum published in the Mol Cell? ,