LncRNA HOTAIR Inhibits miR-19a-3p to Alleviate Foam Cell Formation and Inflammatory Response in Atherosclerosis

Abstract

Background: Atherosclerosis, a chronic inflammatory disease, poses a significant risk for cardiovascular disorders. Meanwhile, emerging evidence suggests that long noncoding RNAs (lncRNAs) play pivotal roles in diverse cardiovascular conditions. Nonetheless, the functional implications of lncRNAs in atherosclerosis remain largely unexplored. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess lncRNA HOTAIR and miR-19a-3p expression levels in patients with atherosclerosis and macrophage-derived foam cells. The release of inflammatory factors was evaluated using enzyme-linked immunosorbent assay (ELISA), while lipid uptake by foam cells was assessed through Oil Red O staining. Additionally, the targeting relationship between lncRNA HOTAIR and miR-19a-3p was validated via a Luciferase reporter assay. Results: LncRNA HOTAIR exhibited downregulation in the plasma of atherosclerosis patients and was found to be inhibited by ox-LDL in human macrophage-derived foam cells. Overexpression of HOTAIR effectively reduced lipid uptake and suppressed the inflammatory response by downregulating the expression of TNF-α and IL-6 during foam cell formation. Mechanistically, HOTAIR mitigated foam cell formation by repressing the expression of miR-19a-3p. Conclusions: In conclusion, our findings, in conjunction with previous studies, elucidate the role of HOTAIR in atherosclerosis. Specifically, we demonstrate that HOTAIR plays a role in alleviating foam cell formation and suppressing the inflammatory response by inhibiting miR-19a-3p in the context of atherosclerosis. Our results suggest the involvement of the TNF-α/miR-19a/HBP1/MIF pathway in mediating these effects. These findings contribute to a better understanding of atherosclerosis's molecular mechanisms and highlight the potential therapeutic implications of targeting HOTAIR and its associated pathways.

The role of HOTAIR in the modulation of resistance to anticancer therapy

“…HOTAIR regulates various physiological cellular processes associated with cell cycle progression, by modulating cell cycle-related protein expressions and inducing cell cycle arrest at the G0/G1 phase ( Zhang et al, 2013 ). Furthermore, HOTAIR can regulate various cell functions by acting as a sponge for multiple miRNAs, thereby reducing their expression and increasing the expression of numerous miRNA targets, including both oncogenes and tumour suppression genes ( Qiu et al, 2022 ; Huang and Xiang, 2023 ; Jiang, Xu and Ren, 2023 ; Le et al, 2023 ; Liu et al, 2023 ; Chen et al, 2024 ). Some miRNAs would, in turn, be capable of binding HOTAIR in a sequence-specific manner and suppressing its expression and functions ( Chiyomaru et al, 2014 ).…”