Abstract
The pathophysiological mechanism of carotid atherosclerosis (CAS) involves endothelial cell dysfunction, vascular smooth muscle cells (VSMCs), and macrophage activation, which ultimately leads to fibrosis of the vessel wall. lncRNA works weightily in the formation of CAS, but the function and mechanism of lncRNA LINC01123 in stable plaque formation are still equivocal. We collected blood samples from 35 CAS patients as well as 33 healthy volunteers. VSMCs treated with oxidized low-density lipoprotein (ox-LDL) were utilized as the CAS cell models. We applied qRT-PCR for detecting LINC01123, miR-1277-5p and KLF5 mRNA expression, CCK-8 method and BrdU test for determining cell proliferation, Transwell test for measuring cell migration, as well as Western blot for assaying KLF5 protein expression. Dual-luciferase reporter experiment was adopted for assessing the interaction between LINC01123 and miR-1277-5p, as well as KLF5 and miR-1277-5p. LINC01123 and KLF5 expression were dramatically up-regulated, while miR-1277-5p expression was down-regulated in CAS patients and ox-LDL-induced CAS cell models. Overexpressed LINC01123 notedly promoted VSMCs migration and proliferation. LINC01123 knockdown repressed cell proliferation and migration. Also, LINC01123 targeted miR-1277-5p and down-regulated its expression, while miR-1277-5p could negatively regulate KLF5 expression. LINC01123 is highly expressed in CAS patients, and promotes cell proliferation and migration via regulating miR-1277-5p/KLF5 axis in ox-LDL-induced VSMCs. It might be involved in the fibrous plaque formation.
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The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
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Provincial Key R&D Program of Hainan (Grant No. ZDYF2019196), National Natural Science Foundation of China (81960227), Natural Science Foundation of Guangdong Province (2017A030313622) and Guangzhou Provincial Program of Science and Technology (201804010446).
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GW and MG conceived and designed the study. YZ and GZ analyzed the data. GZ and YG contributed to the literature review. GW and MG and YG wrote the manuscript. GW and MG reviewed and edited the manuscript. All authors read and approved the final manuscript.
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The experiment was often approved by the Ethics Committee of the Hainan Provincial Hospital of Chinese Medicine, and all patients participating in this study provided written informed consent following the “Helsinki Declaration”.
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Weng, G., Gu, M., Zhang, Y. et al. LINC01123 promotes cell proliferation and migration via regulating miR-1277-5p/KLF5 axis in ox-LDL-induced vascular smooth muscle cells. J Mol Histol 52, 943–953 (2021). https://doi.org/10.1007/s10735-021-10010-4
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DOI: https://doi.org/10.1007/s10735-021-10010-4