LncRNA XIST Promotes Atherosclerosis by Regulating miR-599/TLR4 Axis

Long noncoding RNAs (lncRNAs) have been reported to be implicated in various biological and pathological processes. However, the function and mechanism of XIST in vascular smooth muscle cells (VSMCs) remains unknown. The levels of XIST, miR-599, and TLR4 were tested by RT-qPCR. VSMCs and human monon...

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Bibliographic Details
Published in:Inflammation 2021-06, Vol.44 (3), p.965-973
Main Authors: Yang, Kechun, Xue, Yun, Gao, Xiaoya
Format: Article
Language:English
Subjects:
Apoptosis
Arteriosclerosis
Atherosclerosis
Biomedical and Life Sciences
Biomedicine
Cell culture
Cell proliferation
Cell viability
Cholecystokinin
Immunology
Internal Medicine
Leukocytes (mononuclear)
Low density lipoprotein
Original Article
Pathology
Pharmacology/Toxicology
Rheumatology
Smooth muscle
TLR4 protein
Toll-like receptors
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Summary:Long noncoding RNAs (lncRNAs) have been reported to be implicated in various biological and pathological processes. However, the function and mechanism of XIST in vascular smooth muscle cells (VSMCs) remains unknown. The levels of XIST, miR-599, and TLR4 were tested by RT-qPCR. VSMCs and human mononuclear cells (U937) treated with ox-LDL were used as atherosclerosis (AS) cell models. The CCK-8 assay was adopted to detect cell viability. Cell apoptosis was examined by the TUNEL assay. A dual-luciferase reporter assay was employed to investigate the interaction between miR-599 and XIST or TLR4. In this research, we uncovered that the XIST level was elevated in the serum of AS patients and ox-LDL-treated AS cell models. Functional analysis revealed that XIST depletion restrained cell proliferation, while induced the apoptosis in AS cell models. Besides, miR-599 was verified to be a direct downstream target of XIST and miR-599 inhibitor reversed the effects of XIST knockdown on AS progression. Finally, we demonstrated that XIST increased TLR4 expression by serving as a ceRNA of miR-599. All these findings manifested the role of the XIST/miR-599/TLR4 axis in AS development.
ISSN:0360-3997
1573-2576
DOI:10.1007/s10753-020-01391-x