Down-regulation of long noncoding RNA HULC inhibits the inflammatory response in ankylosing spondylitis by reducing miR-556-5p-mediated YAP1 expression

Abstract

Objective Ankylosing spondylitis (AS) is a progressive systemic disease characterized by a chronic inflammatory response in the sacroiliac joints and spine. Long noncoding RNAs suggest significant actions in the progression of AS. Therefore, a specific lncRNA, highly upregulated in liver cancer (HULC), was studied here regarding its functions and related mechanisms in AS. Methods Measurements of miR-556-5p, HULC, and YAP1 expression were performed on AS cartilage tissues and chondrocytes. The interaction between miR-556-5p and HULC or YAP1 was verified. CCK-8, flow cytometry and enzyme-linked immunosorbent assay were used to evaluate the effects of HULC, miR-556-5p, and YAP1 on the proliferation, apoptosis, and inflammatory response of AS chondrocytes. Furthermore, the action of HULC/miR-556-5p/YAP1 was experimentally observed in AS mice. Results HULC and YAP1 levels were augmented, while miR-556-5p levels were suppressed in AS cartilage tissues and chondrocytes. Downregulating HULC or upregulating miR-556-5p stimulated chondrocyte proliferation and inhibited apoptosis and inflammation in AS. miR-556-5p was a downstream factor of HULC, and YAP1 was a potential target of miR-556-5p. The improvement effect of downregulated HULC on AS chondrocytes was saved when YAP1 expression was forced. In addition, silence of HULC improved the pathological injury of spinal cartilage in AS mice by enhancing miR-556-5p-related regulation of YAP1. Conclusion HULC inhibition relieves the inflammatory response in AS by reducing miR-556-5p-mediated YAP1 expression.

A review of long non-coding RNAs in ankylosing spondylitis: pathogenesis, clinical assessment, and therapeutic targets

“…As previously discussed, HULC has been identified as a potential influencer in the development of AS by regulating the expression of miR-556-5p and YAP1 ( Yi et al, 2023 ). Additionally, elevated levels of HULC and YAP1, coupled with reduced miR-556-5p expression, were observed in the spinal cartilage of AS mice, indicating that HULC contributes to the pathological injury of spinal cartilage.…”

“…A specific lncRNA, highly upregulated in liver cancer (HULC), has been investigated for its functions and related mechanisms in AS ( Yi et al, 2023 ). Their research demonstrated that the silencing of HULC promotes chondrocyte proliferation while reducing apoptosis and inflammation in AS.…”