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. 2023 Feb;26(2):305-315.
doi: 10.1111/1756-185X.14514. Epub 2022 Dec 8.

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

Ping Shao  1 , Huijie Liu  1 , Yanyan Xue  1 , Ting Xiang  1 , Zhanjuan Sun  1
Affiliations

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

Ping Shao et al. Int J Rheum Dis. 2023 Feb.

Abstract

Introduction: 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.

Methods: 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).

Results: 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).

Conclusion: 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.

Keywords: HOTTIP; acute gouty arthritis; diagnostic; inflammation.

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References

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