Mechanism of Long Non-Coding RNA Homeobox Transcript Antisense RNAs Regulates Rheumatoid Arthritis Synovial Fibroblasts Multiplication, Immigration, and Invasion

Long non-coding RNA HOX transcript antisense RNAs (LncRNA HOTAIR) are aberrantly expressed in rheumatoid arthritis synovial fibroblasts (RASFs), the main cells in rheumatoid arthritis (RA). The inhibition, proliferation, and migrative ability of these cells offer one of the most important therapies for RA. To investigate HOTAIR in RA, 72 patients with RA were selected along with 72 healthy volunteers. Serum HOTAIR and miRNA-526b-3p levels were measured in the study groups by qRT-PCR. Following the primary isolation and culture of RASFs, HOTAIR and miRNA-526b-3p expression was detected in RASFs using qRT-PCR and the CCK-8 method was used to measure the cell proliferative capacity. The TNF-alpha and IL-1 beta levels were measured using enzyme-linked immunosorbent assay, while cell motility and invasive capacity were tested by the wound healing assay and transwell chamber assay, respectively. The dual-luciferase reporter assay measured the target-relationship of HOTAIR and miRNA-526b-3p. Western blot detected MMP-2 and MMP-13 protein levels in the samples. We show that serum HOTAIR expression levels were dramatically augmented (P < 0.05) in RA patients compared with the healthy individuals. However, the miRNA526b-3p level was dramatically reduced (P < 0.05). Transfection of si-HOTAIR significantly reduced the OD value of RASFs, while the TNF-alpha level, IL-1 beta level, migration healing rate, MMP-2 protein expression, MMP-13 protein expression (P < 0.05), and the invasive ability were all dramatically debased ( P < 0 .05). HOTAIR could be a competing endogenous RNAs for miRNA-526b-3p. Inhibiting miR-526b-3p expression could dramatically reduce silent HOTAIR on multiplication, immigration, invasion, and inflammatory factor secretion of RASFs. These findings provide evidence that silent HOTAIR inhibits multiplication, immigration, invasion, and inflammatory factor secretion of RASFs by up-regulating the expression of miRNA-526b-3p.

Automated summary

In rheumatoid arthritis (RA), the long non-coding RNA HOTAIR is significantly upregulated while miRNA526b-3p is downregulated in patients compared to healthy individuals. Inhibiting HOTAIR expression can lead to reduced proliferative, migrative, invasive capabilities, and inflammatory factor secretion of RASFs. Therefore, targeting the HOTAIR-miRNA526b-3p axis could be a potential therapeutic strategy for RA.