MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma

Voigtländer, Torsten; Gupta, Shashi; Thum, Sabrina; Fendrich, Jasmin; Manns, Michael P.; Lankisch, Tim O.; Thum, Thomas

doi:10.1371/journal.pone.0139305

Cited by 93 publications

(81 citation statements)

References 42 publications

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“…Few publications, not related to BC, described this miRNA as altered in the serum and bile of cholangioma patients [76], where a speculation of a role for Hsa-miR-1537 in inflammation is proposed.…”

Section: Discussionmentioning

confidence: 99%

How interacting pathways are regulated by miRNAs in breast cancer subtypes

Cava

Colaprico²,

Bertoli

et al. 2016

BMC Bioinformatics

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BackgroundAn important challenge in cancer biology is to understand the complex aspects of the disease. It is increasingly evident that genes are not isolated from each other and the comprehension of how different genes are related to each other could explain biological mechanisms causing diseases. Biological pathways are important tools to reveal gene interaction and reduce the large number of genes to be studied by partitioning it into smaller paths. Furthermore, recent scientific evidence has proven that a combination of pathways, instead than a single element of the pathway or a single pathway, could be responsible for pathological changes in a cell.ResultsIn this paper we develop a new method that can reveal miRNAs able to regulate, in a coordinated way, networks of gene pathways. We applied the method to subtypes of breast cancer. The basic idea is the identification of pathways significantly enriched with differentially expressed genes among the different breast cancer subtypes and normal tissue. Looking at the pairs of pathways that were found to be functionally related, we created a network of dependent pathways and we focused on identifying miRNAs that could act as miRNA drivers in a coordinated regulation process.ConclusionsOur approach enables miRNAs identification that could have an important role in the development of breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1196-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

How interacting pathways are regulated by miRNAs in breast cancer subtypes

Cava

Colaprico²,

Bertoli

et al. 2016

BMC Bioinformatics

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“…Placental Cd levels were significantly associated with increased placental expression of miR-1537 [37]. Little is known about this miRNA, however, it has been suggested to play a role in cancer [49,50]. Interestingly, a recent study examining the relationship between preeclampsia and Cd exposure identified a set of miRNAs common to both preeclampsia and Cd-exposure.…”

Section: Cadmiummentioning

confidence: 99%

Effects of Prenatal Exposure to Endocrine Disruptors and Toxic Metals on The Fetal Epigenome

2017

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Exposure to environmental contaminants during pregnancy has been linked to adverse outcomes at birth and later in life. The link between prenatal exposures and latent health outcomes suggests that these exposures may result in long-term epigenetic reprogramming. Toxic metals and endocrine disruptors are two major classes of contaminants that are ubiquitously present in the environment and represent threats to human health. In this review, we present evidence that prenatal exposures to these contaminants result in fetal epigenomic changes, including altered global DNA methylation, gene-specific CpG methylation and microRNA expression. Importantly, these changes may have functional cellular consequences, impacting health outcomes later in life. Therefore, these epigenetic changes represent a critical mechanism that warrants further study.

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“…Increasing evidences has demonstrated that miRNAs not only regulate various biological processes [16][17][18], but also are associated with the carcinogenesis and progression of diverse human cancers, including CCA [19][20][21]. Serum analysis revealed that miR-1281, miR-126 and miR-30b are significantly higher in CCA patients indicating a potential diagnostic value of these miRNAs in CCA [22]. The miR-17-92 cluster promotes CCA growth by decreasing expression of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) [23].…”

Section: Introductionmentioning

confidence: 96%

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

Kang

Leng

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cholangiocarcinoma (CCA) is one of the most common malignant tumors of the biliary tract originating from biliary epithelial cells. Although many therapeutic strategies have been developed to treat CCA, the survival rate for CCA patients is still quite low. Thus it is urgent to elucidate the pathogenesis of CCA and to explore novel therapeutic targets. miR-191 has been shown to be associated with many human solid cancers, but the function of miR-191 in CCA is still poorly understood. Methods: We first investigated the expression level of miR-191 in human CCA tissues and cell lines with quantitative real-time PCR (qRT-PCR). The effects of miR-191 on CCA cells were determined by Cell Counting Kit-8 assay, colony formation assay and acridine orange/ethidium bromide staining. Finally, we utilized qRT-PCR, western blot and luciferase reporter assays to verify the miR-191 target gene. Results: We showed that miR-191 was up-regulated in CCA cell lines and patients. Knockdown of miR-191 by transfection of its inhibitor sequence blocked RBE cells viability and induced apoptosis of RBE cells. Both qRT-PCR and western blot analysis showed that the secreted frizzled-related protein-1 (sFRP1) level was negatively correlated with that of miR-191. Luciferase assay validated that sFRP1 was a direct target of miR-191. Moreover, knockdown of miR-191 led to suppression of Wnt/β-catenin signaling activation. Co-transfection of sFRP1 small interfering RNA (siRNA) and miR-191 inhibitor re-activated the Wnt/β-catenin signaling pathway as detected by an increased level of β-catenin and phosphorylation of GSK-3β, and restored the expression of survivin and c-myc in RBE cells. Co-transfection of sFRP1 siRNA with miR-191 inhibitor restored the colony formation ability and viability of RBE cells. Conclusion: Taken together, our results demonstrate a novel insight into miR-191 biological function in CCA. Our findings suggest that miR-191 is a potential therapeutic target of CCA treatment.

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MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma

Cited by 93 publications

References 42 publications

How interacting pathways are regulated by miRNAs in breast cancer subtypes

How interacting pathways are regulated by miRNAs in breast cancer subtypes

Effects of Prenatal Exposure to Endocrine Disruptors and Toxic Metals on The Fetal Epigenome

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

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