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Published on: August 14, 2017
circ_0001274 Competitively Binds miR-143-3p to Upregulate VWF Expression to Improve Acute Traumatic Coagulopathy
Yong Luo1,2, Shan Liu2, Qing Li2
1Hengyang Medical School, University of South China, Hengyang 421001, China.
Insights
This study reveals a novel circRNA-microRNA-mRNA network in acute traumatic coagulopathy (ATC). Circ_0001274 upregulates VWF by sponging miR-143-3p, offering a potential therapeutic strategy for ATC.
Area of Science:
- Molecular Biology
- Genetics
- Hematology
Background:
- Competing endogenous RNA (ceRNA) networks involving circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) are implicated in disease pathogenesis.
- Acute traumatic coagulopathy (ATC) is a complex bleeding disorder requiring novel therapeutic targets.
Purpose of the Study:
- To investigate the circRNA-miRNA-mRNA ceRNA regulatory network in the context of ATC.
- To identify key molecular players and their interactions in ATC development and progression.
Main Methods:
- Bioinformatic analysis of online databases and high-throughput circRNA sequencing to identify potential ceRNA networks.
- Experimental validation of the circ_0001274/miR-143-3p/VWF axis in ATC patient samples and mouse models.
- Assays to determine gene expression levels and functional interactions between circ_0001274, miR-143-3p, and VWF.
Main Results:
- Vascular Endothelial Growth Factor (VWF) was identified as a key gene in ATC, exhibiting low expression in patients and mouse models.
- miR-143-3p was found to directly target and inhibit VWF expression.
- circ_0001274 was demonstrated to act as a molecular sponge for miR-143-3p, thereby upregulating VWF expression.
Conclusions:
- The circ_0001274/miR-143-3p/VWF axis plays a critical role in regulating VWF expression in ATC.
- Upregulation of circ_0001274 presents a potential therapeutic strategy for improving outcomes in ATC by restoring VWF levels.
Abstract:
Accumulating evidence has noted the circRNA-microRNA- (circRNA-miRNA-) mRNA competing endogenous RNA (ceRNA) regulatory network in disease development and progression. The current study explored the ceRNA network in acute traumatic coagulopathy (ATC). Potential ATC-related genes were screened, and upstream miRNAs and circRNAs of VWF (the candidate target) were assayed through database searching and high-throughput sequencing technology. circ_0001274/miR-143-3p/VWF ceRNA regulatory network was constructed and validated. The expression of circ_0001274/miR-143-3p/VWF was determined in the peripheral blood samples from ATC patients and ATC mouse models. Online database and circRNA sequencing analysis results identified VWF as a key gene in ATC as supported by assays and that VWF was lowly expressed in ATC patients and mice. Further experiments demonstrated that miR-143-3p could target and inhibit VWF, and circ_0001274 could competitively sponge miR-143-3p. Functionally, circ_0001274 could competitively sequester miR-143-3p to upregulate VWF expression, potentially improving ATC. Our study highlights the critical role of circ_0001274/miR-143-3p/VWF axis in improving ATC.
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