Identification of IFI44L as a new candidate molecular marker for systemic lupus erythematosus.

OBJECTIVES: We screened the type I interferon signal pathway factor involved in the pathogenesis of systemic lupus erythematosus (SLE) by whole-genome sequencing in SLE patients and initially analyse their potential functions. METHODS: Use high-throughput sequencing technology to sequence mRNAs on peripheral blood mononuclear cells from SLE patients and healthy controls,and screen out differentially expressed genes related to the type I interferon (IFN) pathway. Quantitative reverse transcription PCR (RT-qPCR) was utilised to verify the expression of the IFI44L gene in SLE patients and healthy controls, and the correlation between its expression level and clinical test indicators of SLE patients were analysed. The receiver operating characteristic (ROC) analyses were conducted to explore the value of IFI44L for SLE diagnosis. Cell counting kit-8 assay and flow cytometry were used to detect the effects of IFI44L on cell proliferation, apoptosis, and cell cycle. RESULTS: A total of 122 genes were significantly up-regulated and 34 genes were significantly down-regulated in the SLE group compared with the healthy control group in this research. The significantly up-regulated IFI44L in SLE patients was verified by RT-qPCR (p<0.01), furthermore, male SLE patients were significantly higher than that in female SLE patients (p<0.05). Moreover, ROC analyses proved IFI44L may have diagnostic value for SLE. Meanwhile, IFI44L expression level was significantly correlated with platelets, mean platelet volume, red blood cell distribution width to platelet ratio, complement component 3, and C-reactive protein (p<0.05). In addition, under the action of high interferon, IFI44L can resist the proapoptotic effect of IFN-α and improve the proliferation activity of cells. CONCLUSIONS: IFI44L may play an important role in SLE pathology through abnormal regulation of the type I interferon signalling pathway.

MicroRNA-16 inhibits feto-maternal angiogenesis and causes recurrent spontaneous abortion by targeting vascular endothelial growth factor.

Recurrent spontaneous abortion (RSA) is a common health problem that affects women of reproductive age. Recent studies have indicated that microRNAs are important factors in miscarriage. This study investigated the role of miR-16 in regulating vascular endothelial growth factor (VEGF) expression and the pathogenesis of RSA. In this report, clinical samples revealed that miR-16 expression was significantly elevated in the villi and decidua of RSA patients. In vitro, miR-16 upregulation inhibited human umbilical vein endothelial cell proliferation, migration and tube formation. Conversely, the downregulation of miR-16 reversed these effects. In vivo, we demonstrated that abnormal miR-16 levels affect the weights of the placenta and embryo and the number of progeny and microvascular density, as well as cause recurrent abortions by controlling VEGF expression in pregnant mice. VEGF, a potential target gene of miR-16, was inversely correlated with miR-16 expression in the decidua of clinical samples. Furthermore, the luciferase reporter system demonstrated that miR-16 was found to directly downregulate the expression of VEGF by binding a specific sequence of its 3'-untranslated region (3'UTR). Collectively, these data strongly suggest that miR-16 regulates placental angiogenesis and development by targeting VEGF expression and is involved in the pathogenesis of RSA.