Long noncoding RNA LERFS negatively regulates rheumatoid synovial aggression and proliferation
Yaoyao Zou1, Siqi Xu1, Youjun Xiao1
1Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
The Journal of Clinical Investigation
|September 11, 2018
Summary
A novel long noncoding RNA, LERFS, regulates fibroblast-like synoviocytes in rheumatoid arthritis (RA). Decreased LERFS levels promote RA progression, suggesting LERFS as a potential therapeutic target.
Area of Science:
- Molecular Biology
- Rheumatology
- Genetics
Background:
- Fibroblast-like synoviocytes (FLSs) drive joint destruction in rheumatoid arthritis (RA).
- The function of long noncoding RNAs (lncRNAs) in RA pathogenesis is not well understood.
Purpose of the Study:
- To identify and characterize novel lncRNAs involved in RA pathogenesis.
- To investigate the regulatory role of LERFS in FLS function and its potential as a therapeutic target in RA.
Main Methods:
- Identification of LERFS (lowly expressed in rheumatoid fibroblast-like synoviocytes) as a novel lncRNA.
- Investigated the interaction of LERFS with heterogeneous nuclear ribonucleoprotein Q (hnRNP Q).
- Assessed the impact of LERFS on FLS migration, invasion, and proliferation by targeting RhoA, Rac1, and CDC42 mRNA stability and translation.
Main Results:
- LERFS negatively regulates FLS migration, invasion, and proliferation by modulating the stability/translation of RhoA, Rac1, and CDC42 mRNAs via hnRNP Q.
- RA FLSs exhibit decreased LERFS levels, leading to reduced LERFS-hnRNP Q complex formation.
- This reduction enhances target mRNA stability/translation, promoting FLS aggression and contributing to joint destruction in RA.
Conclusions:
- Reduced synovial LERFS expression is implicated in RA pathogenesis and joint damage.
- Targeting the lncRNA LERFS presents a potential therapeutic strategy for rheumatoid arthritis.
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