LncRNA HOTAIR inhibits the progression of fibroblast-like synoviocytes by sponging miRNA-106b-5p in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease of unknown etiology. Human fibroblast-like synoviocytes (HFLSs) are the main effector cells for synovial hyperplasia and invasion in RA. Long non-coding RNAs (lncRNAs) play key roles in several autoimmune diseases, including RA. We investigated the effects of lncRNA HOX transcript antisense intergenic RNA (HOTAIR) on the pathological behavior of HFLSs in RA. The microRNAs (miRNAs) with potential binding sites for lncRNA HOTAIR were predicted using Starbase v2.0. TargetScan (http://www.targetscan.org) was used to analyze the potential target genes of miR-106b-5p. The interactions were further verified using a dual-luciferase reporter assay. RNA and protein expression was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. The proliferation, cell invasion and migration, and cell apoptosis of HFLSs in RA was detected by the 3-(4,5-dimethylthiazol)-2,5-diphenyl-tetrazolium bromide (MTT) assay, transwell assay, and flow cytometry (FCM). The dual luciferase reporter assay confirmed the interactions between lncRNA HOTAIR and miR-106b-5p and between miR-106b-5p and SMAD family member 7 (SMAD7). The qRT-PCR results indicated that the expression of lncRNA HOTAIR was markedly decreased and that of miR-106b-5p was markedly increased in HFLSs of RA. Cell proliferation, invasion, and migration of HFLSs were inhibited by lncRNA HOTAIR upregulation, and the expression of miR-106b-5p was negatively regulated by lncRNA HOTAIR in HFLSs. Apoptosis of HFLS cells was improved by the overexpression of lncRNA HOTAIR. All the effects of lncRNA HOTAIR upregulation on HFLSs were reversed after the overexpression of miR-106b-5p. Smad7 was identified as a target gene of miR-106b-5p, and the effects of downregulation of miR-106b-5p on HFLSs could be abolished by silencing Smad7. We found that lncRNA HOTAIR was significantly downregulated in the HFLSs of patients with RA. Moreover, lncRNA HOTAIR influenced cell growth, migration, invasion, and apoptosis in HFLSs through the miR-106b-5p/Smad7 axis.

Keywords:

• Rheumatoid arthritis
• fibroblast-like synoviocytes
• long non-coding RNAs

Ethics approval and consent to participate

The present study was supported by the Ethics Committee of Xi’an No.5 Hospital. All patients provided the written informed consent.

Consent for publication

All patients provided the written informed consent and agreed for publication.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

The authors declare that they have no competing interests.

Authors’ contributions

Hongxia Qiu contributed to the study design, data collection, statistical analysis, data interpretation, and manuscript preparation. Meixia Liu, Xuefei Shi, Miao Ma, Jing Zhang, and Hua Liu contributed to data collection and statistical analysis. Hongxia Qiu confirmed the authenticity of all the raw data. All authors read and approved the final manuscript.

Additional information

Funding

The present study was supported by the Natural Science Basic Research Program of Shaanxi Province (grant no. 2021JZ-59) and the Xi’an Science and Technology Plan Project (grant no. 2019114913YX004SF037(4)).