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Updated: Mar 26, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-141 inhibits vascular smooth muscle cell proliferation through targeting PAPP-A
Yudong Zhang1, Bainan Chen1, Liu Ming1
1Department of Peripheral Vascular, Affiliated Hospital of Shandong Traditional Chinese Medicine University Jinan, China.
Abstract:
It is well known that ox-LDL plays key roles in the development of atherosclerosis, partly by inducing vascular smooth muscle cells (VSMCs) proliferation. Recent findings have revealed that microRNAs, a class of small noncoding RNAs, could regulate cell proliferation in many physiological and pathological conditions. However, the role and function of miRNAs on ox-LDL induced VSMC proliferation are not fully elucidated. In this study, we showed that ox-LDL could suppress miR-141 expression and inhibition of miR-141 could promote VSMCs proliferation. Moreover, we found that PAPPA was the direct target gene of miR-141. Overexpression of PAPPA impaired the miR-141-induced inhibition of proliferation in the VSMCs. Taken together; miR-141 may play important roles in ox-LDL-induced abnormal proliferation of the VSMC.
Insights
Oxidized low-density lipoprotein (ox-LDL) suppresses miR-141, promoting vascular smooth muscle cell (VSMC) proliferation. Restoring miR-141 or inhibiting its target PAPPA may offer therapeutic strategies for atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- RNA Biology
Background:
- Atherosclerosis involves vascular smooth muscle cell (VSMC) proliferation, often induced by oxidized low-density lipoprotein (ox-LDL).
- MicroRNAs (miRNAs) are regulators of cell proliferation in various conditions, but their specific role in ox-LDL-induced VSMC proliferation remains unclear.
Purpose of the Study:
- To investigate the role and function of specific miRNAs in ox-LDL-induced VSMC proliferation.
- To identify potential molecular targets of these miRNAs in the context of atherosclerosis.
Main Methods:
- Quantitative real-time PCR to measure miR-141 expression.
- Cell proliferation assays to assess VSMC growth.
- Western blotting to detect PAPPA protein levels.
- Luciferase reporter assays to confirm direct targeting of PAPPA by miR-141.
Main Results:
- Ox-LDL treatment significantly suppressed miR-141 expression in VSMCs.
- Inhibition of miR-141 led to increased VSMC proliferation.
- PAPPA was identified as a direct target gene of miR-141.
- Overexpression of PAPPA partially reversed the inhibitory effect of miR-141 on VSMC proliferation.
Conclusions:
- miR-141 plays a critical role in regulating VSMC proliferation under ox-LDL stimulation.
- The miR-141/PAPPA axis is implicated in the pathogenesis of ox-LDL-induced VSMC proliferation.
- Targeting miR-141 or its downstream effectors may represent a novel therapeutic approach for atherosclerosis.
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