RIOK3 potentially regulates osteogenesis-related pathways in ankylosing spondylitis and the differentiation of bone marrow mesenchymal stem cells.

RNA-binding proteins (RBPs), which are key effectors of gene expression, play critical roles in inflammation and immune regulation. However, the potential biological function of RBPs in ankylosing spondylitis (AS) remains unclear. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of five patients with AS and three healthy persons by RNA-seq, obtained differentially expressed RBPs by overlapping DEGs and RBPs summary table. RIOK3 was selected as a target RBP and knocked down in mouse bone marrow mesenchymal stem cells (mBMSCs), and transcriptomic studies of siRIOK3 mBMSCs were performed again using RNA-seq. Results showed that RIOK3 knockdown inhibited the expression of genes related to osteogenic differentiation, ribosome function, and ß-interferon pathways in mBMSCs. In vitro experiments have shown that RIOK3 knockdown reduced the osteogenic differentiation ability of mBMSCs. Collectively, RIOK3 may affect the differentiation of mBMSCs and participate in the pathogenesis of AS, especially pathological bone formation.

Differential lncRNA profiles of blood plasma-derived exosomes from systemic lupus erythematosus.

INTRODUCTION: Long non-coding RNAs (lncRNAs) dysregulation is key in the pathogenesis of systemic lupus erythematosus (SLE), but the role of exosomal lncRNAs in SLE has not been well studied. We elucidated the profiles of plasma exosomal lncRNAs expression in patients with SLE and predictd their potential clinical significance in SLE. METHODS: In the screening stage, six newly diagnosed and untreated patients with SLE and six healthy controls were examined by high-throughput sequencing technology, and differential exosomal lncRNA profiles were constructed. In the validation phase, two differentially selected exosomal lncRNAs from 20 patients each with active and stable SLE and 20 healthy controls were verified with RT-qPCR. The correlation between the selected exosomal lncRNAs and SLE clinical indicators was examined. The diagnostic value of the selected exosomal lncRNAs in SLE was analyzed by the receiver operator characteristic (ROC) curve. RESULTS: Exosomes were successfully extracted from the patients and controls. Sequencing-phase sequencing demonstrated 528 upregulated lncRNAs and 7491 downregulated lncRNAs. In the validation stage, exosomal LINC00667 and DANCR were significantly upregulated in the patients, and positively correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Exosomal DANCR expression between the active and stable SLE patients was different. The area under the curve(AUC) of exosomal LINC00667 and DANCR for SLE diagnosis was 0.815 and 0.759, respectively. CONCLUSIONS: Exosomal LINC00667 and DANCR were upregulated in SLE, and might be new biomarkers thereof. Exosomal DANCR was associated with SLE activity.