Dataset Information

MiR-18a-5p acts as a novel serum biomarker for venous malformation and promotes angiogenesis by regulating the thrombospondin-1/P53 signaling axis.

ABSTRACT: Venous malformation (VM) is a kind of congenital vascular anomaly with high recurrence, and screening for VM lacks an efficient, inexpensive and noninvasive approach now. Serum miRNAs with stable structures are expected to become new postoperative and postablative monitoring biomarkers. Thus, we identified a prognostic serum miR-18a-5p and validated its function in VM. Notably, higher expression level of miR-18a-5p was detected in VM patients than in healthy individuals. We found that miR-18a-5p plays a promotive role in human umbilical vein endothelial cells in vitro. In addition, immunohistochemistry (IHC) results showed a distinct increase of vessels in miR-18a-5p mimics group and a decrease of vessels in inhibitors group compared to the control group in a murine VM model. Furthermore, thrombospondin-1 (TSP1), a potential miR-18a-5p-binding protein, was identified via RNA-seq, luciferase reporter and RNA immunoprecipitation (RIP) assays. Moreover, miR-18a-5p regulated the activation of P53 signaling pathway constituents and consequently led to the regulation of proliferation, migration, invasion and angiogenesis. These results provide a strong theoretical basis for further investigations into pathological mechanism of VM and may provide novel and noninvasive biomarker for VM diagnosis and monitoring.

SUBMITTER: Zhang L

PROVIDER: S-EPMC8581884 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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MiR-18a-5p acts as a novel serum biomarker for venous malformation and promotes angiogenesis by regulating the thrombospondin-1/P53 signaling axis.

Zhang Liming L Wang Deming D Wang Zhenfeng Z Li Xiao X Xia Weiya W Han Yifeng Y Su Lixin L Fan Xindong X

American journal of translational research 20211015 10

Venous malformation (VM) is a kind of congenital vascular anomaly with high recurrence, and screening for VM lacks an efficient, inexpensive and noninvasive approach now. Serum miRNAs with stable structures are expected to become new postoperative and postablative monitoring biomarkers. Thus, we identified a prognostic serum miR-18a-5p and validated its function in VM. Notably, higher expression level of miR-18a-5p was detected in VM patients than in healthy individuals. We found that miR-18a-5p ...[more]

PMID: 34786057

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Project description:Purpose Clear cell renal cell carcinoma(ccRCC) is the most common type of renal cell carcinoma. While it is curable when detected at an early stage, some patients presented with advanced disease have poor prognosis. We aimed to identify key genes and miRNAs associated with clinical prognosis in ccRCC. Methods The microarray datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were analyzed by using GEO2R. Then, Functional enrichment analysis was performed using the DAVID. A retrospective series of 254 ccRCC patients with complete clinical information was included in this study. Kaplan-Meier analysis and multivariate cox regression analysis were used for prognostic analysis. Wound healing assay and transwell assay were designed to evaluate the migration and invasion ability of ccRCC cell lines. Results miRNA-18a was identified to be related with prognosis of ccRCC by using Kaplan-Meier analysis and multivariate cox regression analysis demonstrated that the prognostic value of miRNA-18a was independent of clinical features. Further studies showed that up-regulation of miRNA-18a had a positive effect on migration and invasion of ccRCC cells. The target gene (HIF1A) of the miRNA-18a was predicted by using the miRPathDB database. The transcription factors of DEGs were identified by using the i-cisTarget. Luckily, HIF1A was found to be one of the transcription factors of DEGs. Among these DEGs, PVT1 may be regulated by HIF1A and be related with prognosis of ccRCC. Finally, validation of miRNA18a/HIF1A/PVT1 pathway was checked via reverse transcription-polymerase chain reaction (RT-PCR) assay in both cell lines and clinical tumor samples. Conclusion Our research revealed that miRNA18a/HIF1A/PVT1 pathway might play a crucial role in ccRCC progression, providing novel insights into understanding of ccRCC molecular mechanisms. Importantly, miRNA-18a could serve as a potential diagnostic biomarker and therapeutic targets for ccRCC patients.

Dataset Information

MiR-18a-5p acts as a novel serum biomarker for venous malformation and promotes angiogenesis by regulating the thrombospondin-1/P53 signaling axis.

Publications

MiR-18a-5p acts as a novel serum biomarker for venous malformation and promotes angiogenesis by regulating the thrombospondin-1/P53 signaling axis.

Similar Datasets

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