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KMID : 0578320220450060365
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Molecules and Cells
2022 Volume.45 No. 6 p.365 ~ p.375
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The Molecular Mechanism of Long Non-Coding RNA MALAT1-Mediated Regulation of Chondrocyte Pyroptosis in Ankylosing Spondylitis
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Chen Wei
Wang Feilong
Wang Jiangtao
Chen Fuyu
Chen Ting
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Abstract
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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.
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KEYWORD
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ankylosing spondylitis, chondrocyte, gasdermin D, metastasis-associated lung adenocarcinoma transcript 1, microRNA-558, pyroptosis
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