Department of Orthopaedics, The First People's Hospital of Yongkang, Affiliated to Hangzhou Medical College, Jinhua 321300, China.
Department of Pediatric Orthopaedic, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Mol Cells. 2022 Jun 30;45(6):365-375. doi: 10.14348/molcells.2022.2081.
Long non-coding RNAs (lncRNAs) may be important regulators in the progression of ankylosing spondylitis (AS). The competing endogenous RNA (ceRNA) activity of lncRNAs plays crucial roles in osteogenesis. We identified the mechanism of the differentially expressed lncRNA MALAT1 in AS using bioinformatic analysis and its ceRNA mechanism. The interaction of MALAT1, microRNA-558, and GSDMD was identified using integrated bioinformatics analysis and validated. Loss- and gain-of-function assays evaluated their effects on the viability, apoptosis, pyroptosis and inflammation of chondrocytes in AS. We found elevated MALAT1 and GSDMD but reduced miR-558 in AS cartilage tissues and chondrocytes. MALAT1 contributed to the suppression of cell viability and facilitated apoptosis and pyroptosis in AS chondrocytes. GSDMD was a potential target gene of miR-558. Depletion of MALAT1 expression elevated miR-558 by inhibiting GSDMD to enhance cell viability and inhibit inflammation, apoptosis and pyroptosis of chondrocytes in AS. In summary, our key findings demonstrated that knockdown of MALAT1 served as a potential suppressor of AS by upregulating miR-558 via the downregulation of GSDMD expression.
长链非编码 RNA（lncRNAs）可能是强直性脊柱炎（AS）进展中的重要调节因子。lncRNAs 的竞争性内源性 RNA（ceRNA）活性在成骨中发挥着关键作用。我们通过生物信息学分析及其 ceRNA 机制，确定了差异表达 lncRNA MALAT1 在 AS 中的作用机制。通过整合生物信息学分析鉴定 MALAT1、miR-558 和 GSDMD 的相互作用，并进行了验证。通过缺失和获得功能实验评估了它们对 AS 软骨细胞活力、凋亡、焦亡和炎症的影响。我们发现，AS 软骨组织和软骨细胞中 MALAT1 和 GSDMD 升高，而 miR-558 降低。MALAT1 抑制细胞活力，并促进 AS 软骨细胞的凋亡和焦亡。GSDMD 是 miR-558 的潜在靶基因。抑制 MALAT1 表达可通过抑制 GSDMD 来上调 miR-558，从而增强 AS 软骨细胞的活力，并抑制炎症、凋亡和焦亡。总之，我们的研究结果表明，下调 MALAT1 通过下调 GSDMD 表达来上调 miR-558，从而成为 AS 的潜在抑制因子。
