Regulatory MicroRNA Networks: Complex Patterns of Target Pathways for Disease-Related and Housekeeping MicroRNAs

Zafari, Sachli; Backes, Christina; Leidinger, Petra; Meese, Eckart; Keller, Andreas

doi:10.1016/j.gpb.2015.02.004

Cited by 12 publications

(11 citation statements)

References 24 publications

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“…MicroRNAs (miRNAs) have emerged as crucial players 4 – 7 in regulating gene expression in normal homeostasis and also numerous disorders, including autoimmune, cardiovascular and neurodegenerative diseases and cancer 8 – 10 .…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of Mir-196b in Head and Neck Cancers Leads to Pleiotropic Effects in the Tumor Cells and Surrounding Stromal Fibroblasts

Álvarez-Teijeiro

Menéndez

Villaronga

et al. 2017

Sci Rep

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The miR-196 family members have been found dysregulated in different cancers. Therefore, they have been proposed as promising biomarkers and therapeutic targets. This study is the first to investigate the role of miR-196b in the development and progression of head and neck squamous cell carcinomas (HNSCC), and also the impact on the surrounding tumor microenvironment. Increased miR-196b levels were detected in 95% of primary tumors and precancerous lesions, although no significant differences were observed between non-progressing versus progressing dysplasias. Furthermore, increased levels of both miR-196a and miR-196b were successfully detected in saliva samples from HNSCC patients. The functional consequences of altered miR-196 expression were investigated in both HNSCC cell lines and cancer-associated fibroblasts (CAFs) by transfection with specific pre-miR precursors. Results showed that both miR-196a and miR-196b elicit cell-specific responses in target genes and downstream regulatory pathways, and have a distinctive impact on cell proliferation, migration and invasion. These data reveal the early occurrence and prevalence of miR-196b dysregulation in HNSCC tumorigenesis, suggesting its utility for early diagnosis and/or disease surveillance and also as a non-invasive biomarker in saliva. The pleiotropic effects of miR-196a/b in HNSCC cell subpopulations and surrounding CAFs may complicate a possible therapeutic application.

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Section: Introductionmentioning

confidence: 99%

Dysregulation of Mir-196b in Head and Neck Cancers Leads to Pleiotropic Effects in the Tumor Cells and Surrounding Stromal Fibroblasts

Álvarez-Teijeiro

Menéndez

Villaronga

et al. 2017

Sci Rep

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“…In total, 46 miRNAs were analysed, including 38 prioritised candidate miRNAs (32 in the blood and six in the brain) 14 selected based on our recent systematic review and meta-analysis of over 100 studies and another eight endogenous miRNAs with reportedly stable expression in the blood 35 . Two spike-in controls, UniSp3 and UniSp6, were used as serial quality controls throughout the qPCR process.…”

Section: Methodsmentioning

confidence: 99%

A multi-omics approach identifies a blood-based miRNA signature of cognitive decline in two large observational trials

Sadlon

Takousis

Εvangelou

et al. 2022

Preprint

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Identifying individuals before the onset of overt symptoms is a key prerequisite for the prevention of Alzheimer's disease (AD). A wealth of data reports dysregulated microRNA (miRNA) expression in the blood of individuals with AD, but evidence in individuals at subclinical stages is sparse. In this study, a qPCR analysis of a prioritised set of 38 candidate miRNAs in the blood of 830 healthy individuals from the CHARIOT PRO cohort (West London, UK) was undertaken. Here, we identified six differentially expressed miRNAs (hsa-miR-128-3p, hsa-miR-144-5p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-29c-3p and hsa-miR-363-3p) in the blood of individuals with low cognitive performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A pathway enrichment analysis for the six miRNAs indicated involvement of apoptosis and inflammation, relevant in early AD stages. Subsequently, we used whole genome sequencing (WGS) data from 750 individuals from the AD Neuroimaging Initiative (ADNI) to perform a genetic association analysis for polymorphisms within the significant miRNAs' genes and CSF concentrations of phosphorylated-tau, total-tau, amyloid-β42 and soluble-TREM2 and BACE1 activity. Our analysis revealed 24 SNPs within MIR29C to be associated with CSF levels of amyloid-β42 and soluble-TREM2 and BACE1 activity. Our study shows the potential of a six-miRNA set as diagnostic blood biomarker of subclinical cognitive deficits in AD. Polymorphisms within MIR29C suggest a possible interplay between the amyloid cascade and microglial activation at preclinical stages of AD.

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“…Using miEAA, over 14,000 pathways and other categories were tested sequentially using the two previously described approaches. Targeted gene–miRNA interactions were assessed using miRTargetLink [47] .…”

Section: Methodsmentioning

confidence: 99%

Genome-Wide MicroRNA Expression Profiles in COPD: Early Predictors for Cancer Development

Keller¹,

Fehlmann²,

Ludwig³

et al. 2018

Genomics, Proteomics &Amp; Bioinformatics

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Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer. Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls. Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers. We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type. From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history. Genome-wide miRNA profiles were generated and evaluated using machine learning techniques. For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P < 0.05), including members of the miR-320 family. The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P = 2.3 × 10−5). We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis. For selected miRNAs, qRT-PCR analysis was applied to validate the results. In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer.

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Regulatory MicroRNA Networks: Complex Patterns of Target Pathways for Disease-Related and Housekeeping MicroRNAs

Cited by 12 publications

References 24 publications

Dysregulation of Mir-196b in Head and Neck Cancers Leads to Pleiotropic Effects in the Tumor Cells and Surrounding Stromal Fibroblasts

Dysregulation of Mir-196b in Head and Neck Cancers Leads to Pleiotropic Effects in the Tumor Cells and Surrounding Stromal Fibroblasts

A multi-omics approach identifies a blood-based miRNA signature of cognitive decline in two large observational trials

Genome-Wide MicroRNA Expression Profiles in COPD: Early Predictors for Cancer Development

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