Hsa_circ_0001020 accelerates the lower extremity deep vein thrombosis via sponging miR-29c-3p to promote MDM2 expression
Hsa_circ_0001020 accelerates the lower extremity deep vein thrombosis via sponging miR-29c-3p to promote MDM2 expression
复制标题
Hsa_circ_0001020通过海绵miR-29c-3p促进MDM2表达加速下肢深静脉血栓形成
DOI：
10.1016/j.thromres.2021.12.022
复制
发表时间：
2022-01-20
影响因子：
7.5
通讯作者：
Wang, Bing
中科院分区：
文献类型：
--
作者：
Lou, Zhenkai;Ma, Huan;Wang, Bing
Background: Deep vein thrombosis (DVT) is a serious venous thromboembolism and leads the morbidity and mortality worldwide. Circular RNAs (circRNAs) sever as the important function biomarkers in various diseases, including DVT. However, the regulatory mechanism of circRNAs in DVT remains unclear. Here, we aimed to explore the function and potential mechanism of circRNAs in lower extremity deep vein thrombosis formation in DVT. Methods: QRT-PCR and western blot were performed to detect the expression of hsa_circ_0001020, miR-29c-3p, and MDM2 expression in human peripheral blood of DVT and endothelial progenitor cells (EPCs), respectively. Flow cytometry, RNA FISH and immunofluorescence detected the expression of distribution of circ_0001020 and CD31+ and CD34+ cells. RIP, RNA-pull down, and dual-luciferase reporter gene system were used to determine the binding relationship between hsa_circ_0001020, miR-29c-3p, and MDM2. Wound healing, transwell, and tube formation assays detected cell migration, invasion, and angiogenesis in vitro. DVT mice model was constructed to validate the function of hsa_circ_0001020, and H & E and Carstairs staining were performed to evaluate the pathology of inferior vena cava (IVC). Results: Hsa_circ_0001020 and MDM2 upregulated, whereas miR-29c-3p downregulated in DVT patients and mouse model. Hsa_circ_0001020 sponged miR-29c-3p to promote MDM2 expression thus inhibited EPC migration, invasion and tube formation. And the function of hsa_circ_0001020 and regulatory mechanism was demonstrated by the lose-function of hsa_circ_0001020 and rescue experiment. In DVT mice, hsa_circ_0001020 knockdown suppressed thrombosis and promoted homing ability of EPCs into thrombi. Conclusion: Our finding demonstrated a novel signaling pathway involving hsa_circ_0001020, miR-29c-3p, MDM2, which might be a potential therapeutic target for DVT.
