LncRNA XIST is involved in rheumatoid arthritis fibroblast-like synoviocytes by sponging miR-126-3p via the NF-κB pathway

Abstract

The role and mechanism of lncRNA XIST (XIST) in the development of rheumatoid arthritis (RA) was explored in this study. RT-qPCRs were performed to detect the expression of XIST and miR-126-3p in synovial tissues and cells. Target gene prediction and luciferase gene reporter assay were used to validate downstream target genes of XIST. MTT assay, EdU staining and Annexin V/PI staining were performed to explore the effects of XIST and miR-126-3p on cell proliferation and apoptosis. Western blotting analysis was used to detect the expression of related proteins. We found that the expression levels of XIST in tissues and cells were significantly higher than that in normal tissues and cells. Down-regulation of XIST could inhibit cell proliferation rate and increase apoptosis rate. Luciferase gene reporter assay showed that miR-126-3p was a downstream target gene of XIST. Overexpression of miR-126-3p significantly inhibited RA-FLS cell proliferation and induced RA-FLS cell apoptosis. In addition, down-regulation of XIST could increase the ratio of caspase-3 and Bax/Bcl-2. In addition, overexpression of miR-126-3p could inhibit the NF-κB signalling pathway by reducing the expression levels of p-p65 and p-IκBα in RA-FLS cells. In conclusion, down-regulation of XIST can inhibit the proliferation of synovial fibroblasts by increasing the expression levels of miR-126-3p/NF-κB, thereby inhibiting the occurrence and development of RA.

Keywords:

• Rheumatoid arthritis
• LncRNA XIST
• miR-126-3p
• NF-κB
• apoptosis

Acknowledgments

We thank the financial support from grants (No.81670157) from the National Natural Scientific Foundation of China, grant (No. 2016JZ030) from Natural Scientific Foundation of Shaanxi, Science and technology project of Shanxi Provincial Health Department (201201053) Research Fund of Shanxi overseas study office (2013-122).

Ethical approval

Informed consent was obtained from all individual participants included in the study. All producers were approved by the First hospital of Qiqihar City Ethics Committee. Procedures operated in this research were completed in keeping with the standards set out in the Announcement of Helsinki and laboratory guidelines of research in China.

Author contributions

Wei Liu, Wei Zhong: study concepts, literature research, clinical studies, data analysis, experimental studies, manuscript writing and review; Jing Song: study design, literature research, experimental studies and manuscript editing; Xingyu Feng: definition of intellectual content, clinical studies, data acquisition and statistical analysis; Haolong Yang: data acquisition, manuscript preparation and data analysis.

Disclosure statement

All other authors have no conflicts of interest. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to their containing information that could compromise the privacy of research participants.

Additional information

Funding

Grants [No.81670157] from the National Natural Scientific Foundation of China, grant [No. 2016JZ030] from Natural Scientific Foundation of Shaanxi, Science and technology project of Shanxi Provincial Health Department [201201053], Research Fund of Shanxi Overseas Study Office [2013-122].