Department of Cardiovascular Surgery, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, PR China; Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, PR China.
Department of Cardiovascular Surgery, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, PR China.
Atherosclerosis. 2024 Aug;395:117575. doi: 10.1016/j.atherosclerosis.2024.117575. Epub 2024 May 4.
BACKGROUND AND AIMS: Circular RNA (circRNA) is closely related to atherosclerosis (AS) incidence and progression, but its regulatory mechanism in AS needs further elucidation. AS development is significantly influenced by abnormal vascular smooth muscle cells (VSMCs) growth and migration. This study explored the potential protein role of circLARP1B in VSMC proliferation and migration. METHODS: We performed whole-transcriptome sequencing in human normal arterial intima and advanced atherosclerotic plaques to screen for differentially expressed circRNAs. The sequencing results were combined with database analysis to screen for circRNAs with coding ability. Real-time quantitative polymerase chain reaction was utilized to assess circLARP1B expression levels in atherosclerotic plaque tissues and cells. circLARP1B-243aa function and pathway in VSMCs growth and migration were studied by scratch, transwell, 5-ethynyl-2'-deoxyuridine, cell counting kit-8, and Western blot experiments. RESULTS: We found that circLARP1B was downregulated in atherosclerotic plaque tissue and promoted the proliferation and migration of VSMCs. circLARP1B encodes a novel protein with a length of 243 amino acids. Through functional experiments, we confirmed the role of circLARP1B-243aa in enhancing VSMCs migration and proliferation. Mechanistically, circLARP1B-243aa promotes VSMCs migration and growth by upregulating phosphodiesterase 4C to inhibit the cyclic adenosine monophosphate signaling pathway. CONCLUSIONS: Our results suggested that circLARP1B could promote VSMCs growth and migration through the encoded protein circLARP1B-243aa. Therefore, it could be a treatment target and biomarker for AS.
背景与目的:环状 RNA(circRNA)与动脉粥样硬化(AS)的发生和发展密切相关,但它在 AS 中的调控机制仍需进一步阐明。AS 的发展受到血管平滑肌细胞(VSMCs)异常增殖和迁移的显著影响。本研究旨在探讨 circLARP1B 在 VSMC 增殖和迁移中的潜在蛋白作用。
方法:我们对人正常动脉内膜和进展性动脉粥样硬化斑块进行全转录组测序,以筛选差异表达的 circRNAs。将测序结果与数据库分析相结合,筛选具有编码能力的 circRNAs。采用实时定量聚合酶链反应检测动脉粥样硬化斑块组织和细胞中 circLARP1B 的表达水平。通过划痕、Transwell、5-乙炔基-2'-脱氧尿苷、细胞计数试剂盒-8 和 Western blot 实验研究 circLARP1B-243aa 在 VSMCs 生长和迁移中的功能和途径。
结果:我们发现 circLARP1B 在动脉粥样硬化斑块组织中表达下调,并促进 VSMCs 的增殖和迁移。circLARP1B 编码一种新型蛋白,长度为 243 个氨基酸。通过功能实验,我们证实了 circLARP1B-243aa 在增强 VSMCs 迁移和增殖中的作用。机制上,circLARP1B-243aa 通过上调磷酸二酯酶 4C 抑制环腺苷酸信号通路,促进 VSMCs 的迁移和生长。
结论:我们的研究结果表明,circLARP1B 可通过编码蛋白 circLARP1B-243aa 促进 VSMCs 的生长和迁移。因此,circLARP1B 可能是 AS 的治疗靶点和生物标志物。
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