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 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.

Automated summary

XIST levels were found to be elevated in the serum of AS patients and ox-LDL-treated AS cell models. XIST depletion restrained cell proliferation and induced apoptosis in AS cell models, while miR-599 was identified as a direct downstream target of XIST reversing the effects of XIST knockdown on AS progression. XIST was also shown to increase TLR4 expression by serving as a ceRNA of miR-599, implicating the XIST/miR-599/TLR4 axis in AS development.