RETRACTED: LncRNA HOTAIR alleviates rheumatoid arthritis by targeting miR-138 and inactivating NF-κB pathway
Authors: Hong-Ju Zhang
Qin Geng
Hong-Jie Zhang
Shu-Jun Wang
Xiu-Hua Wang
Xiu-Ying Zhang
Yan-Hui Cui
Qiao-Feng Wei
Journal: International Immunopharmacology (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: HOTAIR; Inflammation; NF-κB signaling pathway; Proliferation; Rheumatoid arthritis
Affiliations: Department of Rheumatology, ZiBo Central Hospital, Zibo 255036, Shandong Province, PR China., The Disease Prevention and Control Center of Zibo, Zibo 255000, Shandong Province, PR China., Department of Rheumatology, The Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong Province, PR China. Electronic address: .

Abstract:  Rheumatoid arthritis (RA) is a chronic and autoimmune-mediated inflammatory disease. We aimed to investigate the regulation of lncRNA HOTAIR in LPS-treated chondrocytes and RA mouse. Our results showed that HOTAIR expression was significantly reduced in LPS-treated chondrocytes. The HOTAIR was then over-expressed in chondrocytes by transfecting recombinant lentivirus carrying sequences encoding HOTAIR. The LPS-induced reduction of cell proliferation rate and production of two inflammatory factors interleukin (IL)-17, IL-23 were markedly inhibited. Enforced expression of HOTAIR also led to the upregulation of proliferation-related protein Ki67 and proliferating cell nuclear antigen (PCNA). Moreover, a negative correlation was detected between the expression of HOTAIR and microRNA (miR)-138, and the expression of miR-138 was significantly increased in LPS-induced chondrocytes. The effects of HOTAIR over-expression on the proliferation and inflammation were partly reversed by miR-138 overexpression. Furthermore, the overexpression of HOTAIR significantly inhibited the activation of nuclear transcription factor-κB (NF-κB) in LPS-treated chondrocytes by suppressing p65 to cell nucleus, resulting in the down-regulation of IL-1β and tumor necrosis factor (TNF)-α. In addition, the in vivo experiments exhibited that overexpression of HOTAIR increased cell proliferation and inhibited inflammation in RA rats, which were demonstrated by upregulation of Ki67 and PCNA, reduced CD4+IL-17+,CD4+IL-23+ cells, and down-regulation of p-p65, IL-1β and TNF-α. In summary, our study suggests HOTAIR plays a protective role in RA by increasing proliferation rate and inhibiting inflammation, which may be related with the regulation of miR-138 expression and NF-κB signaling pathway. These results suggest that the regulation of HOTAIR may be a promising therapeutic strategy for RA. 

Retracted: Yes

PubPeer comments:
 Fig 5D.  HOTAIR promoted cell proliferation and suppressed inflammation in vivo. ... (D) CD4+IL-17+ and CD4+23+ cells were measured by flow cytometry. ![file] The red-boxed panel has appeared in Fig 2C from [Li et al (2016)] . ![] Also Fig 2B from [Wang et al (2017)] , and Fig 2B from [Meng et al (2017)] . Blue-boxed panel is surprisingly similar to a panel from Fig 3A of [Long et al (2017)] . ![file] , 
 Added a green box to 5G ![file] to match 2G of [Li et al (2018)] . ![] UPDATE: also Fig 2G in [Gao et al (2017)] . ![] , 
 Fig 4  (B) The protein expression of Ki67 and PCNA were determined by Western blot. (C) The protein expression of IL-17 and IL-23 were determined by Western blot ![file] Lots of repeated areas in the backgrounds of these  Western blots , manifesting within and between bands. Some of them horizontally reversed. Other  WBs are left as an exercise for the reader. , 
 This is a serious problem . Due to our lack of strict control lead to such unreal pictures appeared. We immediately applied to the magazine to retract the manuscript, and apologized for the serious negative effection caused by this, and thank you very much for your supervision and support! , 
 Retracted [3 March 2021] . The corresponding author has my sympathy, and my admiration for the prompt and appropriate response.  This article has been retracted at the request of corresponding author Xiu-hua Wang given allegations regarding the credibility of the flow cytometry and western blotting images in the paper. The authors would like to clarify the allegations about the credibility of Figure 5D and Figure 4B however, since the experiment and the corresponding data analysis were outsourced to other institutions, the authors could not double check these images. Thus, the corresponding author asked that the paper be retracted, and the authors will make more efforts to verify the conclusion of the paper. All authors agree to the Retraction. ,