Induced MiR-1249 expression by aberrant activation of Hedegehog signaling pathway in hepatocellular carcinoma

Ye, Yibiao; Wei, Yunping; Xu, Yunxiuxiu; Li, Yanshan; Wang, Ruomei; Chen, Jie; Zhou, Yu; Fu, Zhiqiang; Chen, Yan; Wang, Xin; Yu, Ruiping; Bai, Chunling; Li, Guangpeng; Chen, Rufu; Chen, Tao

doi:10.1016/j.yexcr.2017.03.010

Cited by 19 publications

(10 citation statements)

References 26 publications

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“…In addition, the involvement of miR-1249-3p has also been described in liver cancer based on two independent studies. The first study reported the downregulated expression of miR-1249-3p in tumor tissues [36], whereas the second study observed that elevated levels of miR-1249-3p in hepatocellular carcinoma tissues from patients were correlated with a poorer prognosis [37]. MiR-6869-5p may act as a tumor suppressor and has been identified as a potential prognostic biomarker for colorectal cancer [38].…”

Section: Discussionmentioning

confidence: 99%

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

Loke

Munusamy

Koh

et al. 2019

Cancers

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Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to avoid subjecting patients with abnormal mammograms to unnecessary follow-up diagnostic procedures. Serum samples from 116 malignant breast lesions and 64 benign breast lesions were comprehensively profiled for 2,083 microRNAs (miRNAs) using next-generation sequencing. Of the 180 samples profiled, three outliers were removed based on the principal component analysis (PCA), and the remaining samples were divided into training (n = 125) and test (n = 52) sets at a 70:30 ratio for further analysis. In the training set, significantly differentially expressed miRNAs (adjusted p < 0.01) were identified after correcting for multiple testing using a false discovery rate. Subsequently, a predictive classification model using an eight-miRNA signature and a Bayesian logistic regression algorithm was developed. Based on the receiver operating characteristic (ROC) curve analysis in the test set, the model could achieve an area under the curve (AUC) of 0.9542. Together, this study demonstrates the potential use of circulating miRNAs as an adjunct test to stratify breast lesions in patients with abnormal screening mammograms.

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Section: Discussionmentioning

confidence: 99%

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

Loke

Munusamy

Koh

et al. 2019

Cancers

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“…Here we demonstrate that miR‐1249‐5p acts as a negative regulator of liver inflammatory response by directly targeting MCP‐1. MiR‐1249 has been reported to be aberrantly expressed and closely associated with tumor growth, metastasis and angiogeneiss by targeting VEGFA and HMGA2 in hepatocellular carcinoma [32, 33]. However, the function of miR‐1249 in MCP‐1 expression and liver inflammation remains unknown and is first documented in the current study.…”

Section: Discussionmentioning

confidence: 73%

Sphingosine 1‐phosphate/microRNA‐1249‐5p/MCP‐1 axis is involved in macrophage‐associated inflammation in fatty liver injury in mice

Yang

Zhang

et al. 2020

Eur J Immunol

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Monocyte chemotactic protein‐1 (MCP‐1) is one of the most representative inflammatory cytokines, and has been proved to be markedly increased in injured liver and sphingosine 1‐phosphate (S1P)‐treated macrophages. However, microRNAs (miRNAs) targeting MCP‐1 and the role of miRNA/MCP‐1 axis in S1P‐mediated liver inflammation remain largely unknown. Here, we demonstrate that MCP‐1 expression is increased in the liver and isolated liver macrophages of MCDHF mice. Moreover, there is a positive correlation between the hepatic levels of S1P and MCP‐1. We then predict miRNAs targeting MCP‐1 by bioinformatics analysis and select miRNA‐1249‐5p (miR‐1249‐5p) from the intersection of TargetScan database and downregulated miRNAs in the injured liver. S1P significantly upregulates the expression of MCP‐1 and decreases miR‐1249‐5p expression in macrophages. MiR‐1249‐5p directly targets 3’‐UTR of MCP‐1 and negatively regulates its expression in S1P‐treated macrophages. Administration of miR‐1249‐5p agomir decreases hepatic MCP‐1 levels and attenuates liver inflammation in MCDHF mice. Protein‐protein interaction network by STRING displays that S1P system is closely associated with MCP‐1/CCR2 axis in the network of inflammation. In conclusion, we characterize the vital role of miR‐1249‐5p in negatively regulating MCP‐1 expression in vitro and in vivo, which may open new perspectives for pharmacological treatment of liver disease.

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“…Therefore, investigating a single factor associated with gene regulation is not sufficient to assess the prognosis of patients with HCC. Previous studies have identified genes that regulate HCC progression; however, the majority of these studies focused on single genes or investigated only one of the factors influencing gene regulation (16)(17)(18), without considering their combinatorial effect. To understand the complex molecular biological characteristics of HCC, differentially expressed lncRNAs, miRNAs and mRNAs were identified by analyzing biological datasets from TCGA database.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of the interactions among lncRNA, miRNA and mRNA expression, genetic mutations and epigenetic modifications in hepatocellular carcinoma

Lin

Yuan

et al. 2018

Mol Med Report

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The present study aimed to investigate the regulatory networks involving long noncoding RNA (lncRNA), microRNA (miRNA), mRNA, genetic mutations and epigenetic modifications in hepatocellular carcinoma (HCC) by analyzing datasets from The Cancer Genome Atlas (TCGA) database. TCGA was mined, and miRNAs, lncRNAs and mRNAs that were differentially expressed in HCC were identified using R software. A gene regulatory network was constructed using Cytoscape software. Representative genes were selected for functional enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The associations among various proteins and protein networks were identified using the online software Search Tool for the Retrieval of Interacting Genes/Proteins. The cBioPortal database was used to analyze the association between genetic mutations and epigenetic modification, and the development of HCC. A total of 35 mRNAs were predicted to be targeted by 77 lncRNAs and 16 miRNAs, establishing a lncRNA-miRNA-mRNA regulatory network for HCC. Multivariable Cox regression analysis suggested that long intergenic non-protein coding RNA 200, miRNA-137, PDZ binding kinase and DNA polymerase θ were independent prognostic factors. In a regulatory network centered on miRNA-424, six mRNA target genes were associated with HCC survival rates. Protein-protein interaction analysis suggested that cell division cycle 25A (CDC25A) interacted with centrosomal protein 55 (CEP55), claspin, E2F transcription factor 7 and cyclin E1 (CCNE1. Mutations in CEP55 affected overall survival and disease-free survival in HCC, whereas, mutations in CDC25A affected overall survival, and mutations in E2F7 affected disease-free survival. Decreased methylation levels of CEP55, CDC25A and CCNE1 were associated with vascular invasion. The survival rate of patients with hypermethylation of CCNE1 and CEP55 was significantly associated with the rate of methylation of these loci. The present study provides an integrated bioinformatics analysis of gene expression, genetic mutations and epigenetic modifications that may be associated with the development of HCC.

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Induced MiR-1249 expression by aberrant activation of Hedegehog signaling pathway in hepatocellular carcinoma

Cited by 19 publications

References 26 publications

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

Sphingosine 1‐phosphate/microRNA‐1249‐5p/MCP‐1 axis is involved in macrophage‐associated inflammation in fatty liver injury in mice

Bioinformatics analysis of the interactions among lncRNA, miRNA and mRNA expression, genetic mutations and epigenetic modifications in hepatocellular carcinoma

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