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

Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101213954 Publication Model: eCollection Cited Medium: Internet ISSN: 1449-1907 (Electronic) Linking ISSN: 14491907 NLM ISO Abbreviation: Int J Med Sci Subsets: MEDLINE

Original Publication: [Australia] : Ivyspring International Publisher, c2004-

Atherosclerosis*/genetics ; Cardiovascular Diseases* ; MicroRNAs*/genetics ; RNA, Long Noncoding*/genetics; Humans ; Foam Cells ; High Mobility Group Proteins ; Repressor Proteins ; Tumor Necrosis Factor-alpha/genetics

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.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
(© The author(s).)

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Keywords: Atherosclerosis; Foam cell; Inflammatory factor; LncRNA

0 (HBP1 protein, human)
0 (High Mobility Group Proteins)
0 (MicroRNAs)
0 (Repressor Proteins)
0 (RNA, Long Noncoding)
0 (Tumor Necrosis Factor-alpha)
0 (HOTAIR long untranslated RNA, human)
0 (MIRN19 microRNA, human)

Date Created: 20240122 Date Completed: 20240216 Latest Revision: 20240216

20240217

PMC10797679

10.7150/ijms.90315

38250607