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. 2023 Jun 16;16(1):134.
doi: 10.1186/s12920-023-01563-2.

MicroRNA-361-5p acts as a biomarker for carotid artery stenosis and promotes vascular smooth muscle cell proliferation and migration

Fei Wang  1 , Yumei An  2 , Huihui Hao  3
Affiliations

MicroRNA-361-5p acts as a biomarker for carotid artery stenosis and promotes vascular smooth muscle cell proliferation and migration

Fei Wang et al. BMC Med Genomics. .

Abstract

Background: Vascular smooth muscle cells (VSMCs) dysfunction participates in carotid artery stenosis (CAS). The study aimed to examine the expression pattern of miR-361-5p in CAS patients, and explore its role in VSMCs proliferation and migration.

Methods: qRT-PCR was performed for the detection of miR-361-5p in serum samples of 150 CAS cases and 150 healthy people. Multiple logistic regression analysis and receiver operating characteristic (ROC) curve was accomplished to detect diagnostic value via SPSS 21.0 statistical software. Cell function of VSMCs was evaluated. Target association was predicted through bioinformatic analysis and confirmed via luciferase activity.

Results: Serum miR-361-5p was enhanced in CAS cases and was positively correlated with CAS degree. Logistic regression analysis determined the independent influence of miR-361-5p in CAS, and ROC curve demonstrated its diagnostic value with AUC of 0.892. miR-361-5p promoted VSMCs proliferation and migration, but the influence was counteracted by TIMP4.

Conclusions: MiR-361-5p is a promising biomarker for CAS, and can be used as a potential target for early diagnosis and treatment of CAS. MiR-361-5p can promote VSMCs proliferation and migration via targeting TIMP4.

Keywords: Carotid artery stenosis; MicroRNA-361-5p; ROC; VSMCs.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Expression pattern of miR-361-5p in CAS cases. A. Elevated level of miR-361-5p was detected in the serum of CAS cases in comparison with the control group. B. High values of serum miR-361-5p was determined in severe CAS group. C. Correlation of serum miR-361-5p with the CAS degree score. *** P < 0.001
Fig. 2
Fig. 2
Clinical value of miR-361-5p for CAS. A. Multiple logistic regression analysis results of clinical factors related to CAS and the forest plot. B. ROC curve of serum miR-361-5p in differentiating CAS from healthy people
Fig. 3
Fig. 3
MiR-361-5p promotes VSMCs proliferation and migration. A. MiR-361-5p levels in cells after transfected with miR-361-5p mimic or inhibitor. B. Cell proliferation of cells after transfected with miR-361-5p mimic or inhibitor. C. Cell migration of cells after transfected with miR-361-5p mimic or inhibitor. *** P < 0.001 vs. control group
Fig. 4
Fig. 4
TIMP4 serves as the target gene of miR-361-5p. A. The Venn diagram displayed the intersection genes based on the data from TargetScan, miRDA and GeneCards. B. The binding sites between miR-361-5p and TIMP4 was predicted by TargetScan. C. Cell luciferase activity of cells after transfected with miR-361-5p mimic or inhibitor. *** P < 0.001 vs. mock group. D. Decreased TIMP4 mRNA levels in the serum of CAS cases. E. Decreased TIMP4 protein levels in the serum of CAS cases. *** P < 0.001
Fig. 5
Fig. 5
TIMP4 knockdown counteracts the role of miR-361-5p in VSMCs. A. TIMP4 mRNA levels in cells after transfected with miR-361-5p inhibitor or si-TIMP4. B. Cell proliferation of cells after transfected with miR-361-5p inhibitor or si-TIMP4. C. Cell migration of cells after transfected with miR-361-5p inhibitor or si-TIMP4. *** P < 0.001 vs. inhibitor NC group; ### P < 0.001 vs. miR-361-5p inhibitor group
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