LncRNA HOTTIP promotes inflammatory response in acute gouty arthritis via miR-101-3p/BRD4 axis.

Abstract

Acute gouty arthritis (AGA) is characterized by the accumulation of pro-inflammatory factors. This research aimed to examine the regulation of long non-coding RNA HOXA distal transcript antisense RNA (HOTTIP) in AGA on inflammation and its potential mechanisms. Serum levels of HOTTIP in AGA patients were examined by reverse-transcription quantitative polymerase chain reaction. The receiver operating characteristic curve was performed in the diagnosis of AGA patients. Monosodium urate (MSU) stimulation of THP-1-derived macrophages was used to establish an in vitro AGA model. Enzyme-linked immunosorbent assay was carried out to assess the levels of pro-inflammatory cytokines. Pearson correlation was applied to examine the correlation. RNA immunoprecipitation assay and dual-luciferase reporter assay were employed to identify the targeting relationship between miR-101-3p and HOTTIP or bromodomain-containing 4 (BRD4). HOTTIP and BRD4 were statistically overexpressed in AGA patients compared with controls, while miR-101-3p was reduced (P < 0.05). Serum HOTTIP can significantly distinguish AGA patients from healthy controls. HOTTIP bound with miR-101-3p then augmented BRD4 via a competing endogenous RNA mechanism. Additionally, HOTTIP levels were elevated in a dose-dependent manner by MSU (P < 0.05). Weakened HOTTIP significantly inhibited MSU-induced release of pro-inflammatory factors interleukin (IL)-1β, IL-8, and transforming growth factor-α in macrophages (P < 0.05), but this inhibition was reversed by silencing miR-101-3p (P < 0.05). In short, HOTTIP contributes to inflammation via miR-101-3p/BRD4 axis, and serves as a new diagnostic biomarker. This study offers a renewed perspective on the diagnosis and treatment of AGA.