Overexpressed microRNA-103a-3p inhibits acute lower-extremity deep venous thrombosis via inhibition of CXCL12.

Studies have shown that microRNAs (miRNAs) participate in almost all pathological and physiological processes including acute lower-extremity deep venous thrombosis (LEDVT). Here, this study was designed to elucidate the possible function of miR-103a-3p in acute LEDVT. Expression of miR-103a-3p and chemokine C-X-C motif ligand 12 (CXCL12) was initially quantified in plasma collected from 81 LEDVT patients. Then LEDVT mouse models were established by injection with 3% sodium pentobarbital. The interaction between miR-103a-3p and CXCL12 was identified by dual-luciferase reporter gene assay. After gain- and loss-of-function studies, interleukin-6 (IL-6) and IL-8 and tissue factor (TF) levels, and expression of plasminogen activator inhibitors (PAIs), von Willebrand factor (vWF), thromboxane A2 (TH-A2), F4/80, IL-12, Arginase-1 (Arg-1) and CD206 were determined using enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. miR-103a-3p was downregulated, while CXCL12 was upregulated in patients and mice with LEDVT. miR-103a-3p targets CXCL12 and inhibited its expression. Overexpressed miR-103a-3p or downregulated CXCL12 decreased expression of IL-6, IL-8, TF, PAIs, vWF, TH-A2, M1 markers (IL-6 and IL-12), yet increased expression of M2 markers (Arg-1 and CD206) in LEDVT mice. Additionally, upregulated miR-103a-3p or silencing CXCL12 suppressed thrombosis in LEDVT mice. However, overexpression of CXCL12 reversed the tendency mentioned above. Altogether, miR-103a-3p can potentially downregulate CXCL12 expression to disrupt inflammatory response and thrombosis, ultimately preventing the development of LEDVT. Our findings underscore a possible alternative therapeutic strategy to limit LEDVT.

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