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

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Abstract

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.

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Data Availability

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

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Acknowledgments

We are grateful to all the participants in this work.

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Authors and Affiliations

  1. Department of Endocrinology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, No. 68, Gehu Road, Changzhou, 213161, China

    Kechun Yang, Yun Xue & Xiaoya Gao

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  1. Kechun Yang
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  2. Yun Xue
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  3. Xiaoya Gao
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Contributions

KY as the first author contributed significantly to analysis and manuscript preparation. XG as the corresponding author contributed to the conception of the study. KY, YX, and XG helped perform the analyses with constructive discussions. All authors read and approved the manuscript and agree to be accountable for all aspects of the research in ensuring that the accuracy or integrity of any part of the work is appropriately investigated and resolved.

Corresponding author

Correspondence to Xiaoya Gao.

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Competing Interests

The authors declare that they have no competing interests.

Ethics Approval and Consent to Participate

The study protocol was approved by the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, and all patients provided written informed consent. All of the procedures were in compliance with The Declaration of Helsinki and relevant policies in China.

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Not applicable.

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Yang, K., Xue, Y. & Gao, X. LncRNA XIST Promotes Atherosclerosis by Regulating miR-599/TLR4 Axis. Inflammation 44, 965–973 (2021). https://doi.org/10.1007/s10753-020-01391-x

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  • DOI: https://doi.org/10.1007/s10753-020-01391-x

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