NF-κB-Regulated miR-99a Modulates Endothelial Cell Inflammation

Abstract

Objective. The present study was performed to investigate the effects and mechanisms of miR-99a on LPS-induced endothelial cell inflammation, as well as the regulation of NF-κB on miR-99a production. Methods and Results. ELISA showed that LPS treatment significantly promoted the secretion of inflammatory factors (TNF-α, IL-6, IL-1β, and MCP-1). LPS treatment also inhibited miR-99a production and promoted mTOR expression and NF-κB nuclear translocation. Overexpression of miR-99a suppressed the LPS-induced TNF-α, IL-6, IL-1β, and MCP-1 overproduction, mTOR upregulation, and NF-κB nuclear translocation. The PROMO software analysis indicated NF-κB binding site in the −1643 to −1652 region of miR-99a promoter. Dual luciferase reporter analysis, electrophoretic mobility shift assays (EMSA), and chromosome immunoprecipitation (ChIP) assays demonstrated that NF-κB promoted the transcription of miR-99a by binding to the −1643 to −1652 region of miR-99a promoter. Further studies on HUVECs verified the regulatory effects of NF-κB on miR-99a production. Conclusion. MiR-99a inhibited the LPS-induced HUVECs inflammation via inhibition of the mTOR/NF-κB signal. NF-κB promoted miR-99a production by binding to the −1643 to −1652 region of miR-99a promoter. Considering the importance of endothelial inflammation on cardiovascular diseases, such as atherosclerosis, our results may provide a new insight into the pathogenesis and therapy of atherosclerosis.

miR-130a upregulates mTOR pathway by targeting TSC1 and is transactivated by NF-κB in high-grade serous ovarian carcinoma

“…However, another study demonstrated that miR-99a inhibited the mTOR expression, suppressed the nuclear translocation of NF-κB, and resulted in the attenuation of inflammation. 24 miRNAs are involved in regulation of autophagy. miR-30a could negatively regulate autophagic activity through targeting Beclin1.…”

Comprehensive Profiling of the Circulatory miRNAome Response to a High Protein Diet in Elderly Men: A Potential Role in Inflammatory Response Modulation

“…Yet its precise function is not established, as miR‐99a has been shown to regulate many processes including cell proliferation, apoptosis and inflammation . miR‐99a appears to target both the IL6/STAT3 and mTOR/NF‐κB signaling pathways . Therefore, downregulated expression of miR‐99a in 2RDA group suggests possible complex functionality, including involvement in inflammatory responses and cell proliferation or anabolism.…”

Combined Analysis of Human and Experimental Murine Samples Identified Novel Circulating MicroRNAs as Biomarkers for Atrial Fibrillation

“…An accumulation of evidence from several studies has shown that miR-99a regulates the expression of mammalian target of rapamycin (MTOR), resulting in suppression of the nuclear translocation of nuclearfactor κB (NF-κB) to attenuate inflammation. 35, 36 It has also been reported that EZH1 and EZH2 are the targets of miR-214-3p, possibly contributing to cardiac fibrosis. 37 As for miR-342-5p, TGF-β signaling was attenuated by it.…”

“…28 The HUNT study showed that several miRNAs in serum were associated with a future acute myocardial infarction (AMI), and proposed that a panel using 5 miRNAs (miR-106a-5p, miR-424-5p, let-7 g-5p, miR-144-3p, and tion. 35, 36 Regarding miR-214, Chen et al revealed that miR-214 overexpression enhanced the expression of IL-6 and TNF-α under conditions of viral myocarditis. 42 However, some other reports have suggested that miR-214 works to suppress inflammation.…”