MiR-24-3p Inhibits Migration and Proliferation of HUVECs by Downregulating CHI3L1

MiR-24-3p Inhibits Migration and Proliferation of HUVECs by Downregulating CHI3L1

Guanjun Wu,¹ Lei Gao,² Xin Zhang,¹ Qi Xue,¹ Lifang Ye,¹ Yaru Zheng¹ and Jianlei Zheng^1,2,3

¹Department of Cardiovascular Medicine, Heart Center, Zhejiang Provincial People’s Hospital/People’s Hospital of Hangzhou Medical College, Hangzhou, China
²Graduate school, Bengbu Medical University, Bengbu, Anhui, China
³Department of Cardiology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China

Angiogenesis is regarded as a critical factor in the pathogenesis of unstable atherosclerotic plaques, and numerous proteins and microRNAs (miRNAs) were involved in this process. In our previous study, the overexpression of Chitinase 3-like 1 (CHI3L1) aggravates the neo-vessels in carotid plaques of apoE^-/- mice fed with a high-fat diet. MiR-24-3p is one of target miRNAs adjusting the expression of CHI3L1. Extracellular signal-regulated kinase (ERK) signaling pathway is an important regulator related to cell proliferation and pathophysiological process of CHI3L1. This study aims to investigate whether the miR-24-3p plays a role in migration and proliferation of human umbilical vein endothelial cells (HUVECs) through influencing the expression of CHI3L1 and potential molecular mechanism. CCK8 assay, transwell and matrigel tests were used to determine the effects of miR-24-3p on proliferation, migration and tube formation of HUVECs by targeting CHI3L1. Luciferase assay was carried out to value the direct interaction between miR-24-3p and CHI3L1 3′-untranslated region (3′-UTR). Western blot was used to measure protein expression of CHI3L1, ERK and phosphorylation of ERK (p-ERK). This study demonstrated that miR-24-3p mimic inhibits the proliferation, migration and angiogenesis of HUVECs. The role of miR-24-3p affects the function of HUVECs through negative regulation of CHI3L1 expression targeting CHI3L1 3′-UTR. Furthermore, we found that p-ERK was accordant with CHI3L1 expression in HUVECs, and miR-24-3p mimics significantly diminished the CHI3L1 expression and the level of p-ERK. MiR-24-3p is one of miRNAs regulating the expression and function of CHI3L1, which may provide an efficient strategy for treatment of angiogenesis in atherosclerotic plaques.

Key words —— angiogenesis; chitinase 3-like 1; human umbilical vein endothelial cells; miR-24-3p; signaling pathway

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Tohoku J. Exp. Med., 2025 April, 265(4), 271-278.

Correspondence: Jianlei Zheng, Department of Cardiology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

e-mail: zhengjianlei@sysush.com