MicroRNA-139, an Emerging Gate-Keeper in Various Types of Cancer

Stavast, Christiaan J.; Zuijen, Iris van; Erkeland, Stefan J.

doi:10.3390/cells11050769

Cited by 6 publications

(5 citation statements)

References 126 publications

(185 reference statements)

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“…In this group, miRNA-150 and miR-139 were significantly elevated compared to non-drinkers ( Figure 3 ). MiR-150 is suggested to play a protective role in the heart [ 84 ], while MiR-139 is discussed as gate-keeper in cancer while acting against different types of stress, including DNA damage [ 85 ]. This may indicate a specific regulatory pathway through which moderate alcohol consumption exerts its protective effects on heart health.…”

Section: Discussionmentioning

confidence: 99%

Lifestyle-Driven Variations in Nutrimiromic MicroRNA Expression Patterns across and beyond Genders

Pointner,

Krammer,

Tomeva

et al. 2024

Life

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The importance of diet and lifestyle in maintaining overall health has long been recognised. MicroRNAs (miRNAs) have emerged as key players in the intricate interplay between health and disease. This study, including 305 participants, examined the role of miRNAs from capillary blood as indicators of individual physiological characteristics, diet, and lifestyle influences. Key findings include specific miRNAs associated with inflammatory processes and dietary patterns. Notably, miR-155 was associated with subjects with metabolic diseases and upregulated in age. Additionally, the study revealed diet-related miRNA expressions: high consumption of vegetables, fruits, and whole grains correlated with increased levels of miR-let-7a and miR-328, both implicated in anti-inflammatory pathways, and decreased expression of pro-inflammatory miR-21. In the context of smoking, we found a significant decrease in miRNA-142, known for its downregulation in lung cancer. We observed a sex-biased expression of various miRNAs with significant upregulation of miR-151a in females and a higher expression of miR-155 in ageing females, representing a possible mechanism for the increased susceptibility to autoimmune diseases. In conclusion, the study underscores the significant influence of lifestyle, nutrition, and sex on miRNA profiles. Circulating miRNAs demonstrate significant potential as biomarkers in personalized medicine, highlighting their utility in tailoring healthcare to individual needs.

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Section: Discussionmentioning

confidence: 99%

Lifestyle-Driven Variations in Nutrimiromic MicroRNA Expression Patterns across and beyond Genders

Pointner,

Krammer,

Tomeva

et al. 2024

Life

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“…[66][67][68] It is worth mentioning that, by contrast to ACC, miR-139-5p is underexpressed in AML, GC and CRC and acts as a tumour-suppressor miRNA in many cancers. 69,70 To strengthen our observations in vitro, we analyzed the relationship between Wnt/β-Catenin pathway mutational status and miR-139-5p levels in ACC patients. Importantly, we found that patients with mutations have significantly higher levels of PDE2A and miR-139-5p and a significantly lower level of NDRG4 when compared to patients with no known mutation in the Wnt/β-Catenin pathway.…”

Section: Discussionmentioning

confidence: 99%

“…66-68 It is worth mentioning that, by contrast to ACC, miR-139-5p is underexpressed in AML, GC and CRC and acts as a tumour-suppressor miRNA in many cancers. 69, 70…”

Section: Discussionmentioning

confidence: 99%

Aberrant activation of Wnt/β-Catenin signaling pathway drives the expression of poor prognosis-associated microRNAs in adrenocortical cancer with a major impact on miR-139-5p and its host gene PDE2A

Cristante

Sayed

Denis

et al. 2023

Preprint

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Adrenocortical carcinoma (ACC) is a rare malignancy with dismal prognosis. Deregulated microRNA (miRNA) expression has been implicated in ACC aggressiveness. Nevertheless, the mechanisms underlying such deregulations remain unknown. Aberrant Wnt/β-Catenin signaling has been reported in about 40% of ACC and is associated with poor outcome. Here, we investigated the link between constitutive activation of Wnt/β-Catenin pathway and miRNA expression alterations in ACC. Inducible shRNA-mediated gene silencing of β-Catenin (β-Cat) was performed in ACC cells expressing constitutively active β-Catenin. The miRnome of ACC cells was analyzed using RNA-Sequencing. Selected miRNAs and mRNAs were validated using quantitative PCR and functional experiments with an emphasis on miR-139-5p, its host gene phosphodiesterase 2A (PDE2A) and its target gene N-Myc Downstream-Regulated Gene 4 (NDRG4). Prognostic values of Wnt/β-Catenin pathway components or mutational status and their correlations with miRNA/mRNA expressions were determined in COMETE-ENSAT and TCGA cohorts. We carried out the first miRnome analysis in β-Catenin-deficient (β-Cat-) ACC cells. Twelve upregulated miRNAs and 42 downregulated miRNAs among which miR-139-5p and miRNAs of the 14q32 locus were identified in β-Cat- cells. Downregulation of selected poor prognosis-associated miRNAs was confirmed using RT-qPCR. Remarkably, the expression of the intronic miR-139-5p was decreased by 90% in β-Cat- cells with a concomitant repression of its host gene PDE2A and upregulation of its target gene NDRG4. In ACC patients, miR-139-5p levels were highly correlated with the levels of PDE2A and anti-correlated with those of NDRG4. MiR-139-5p and PDE2A expressions were higher in patients with mutations in components of Wnt/β-Catenin signaling pathway or high expression of LEF1, with LEF1 proving a better predictor of prognosis than Wnt/β-Catenin signaling pathway mutational status. Our findings indicate that in addition to inducing protein-coding genes in ACC, constitutively active Wnt/β-Catenin signaling upregulates the expression of a subset of miRNAs involved in tumour aggressiveness and poor clinical outcome.

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“…Numerous reports of altered miRNA expression have been linked to various pathologies [ 11 , 12 , 13 ], including BC [ 14 , 15 ]. MiRNAs are small non-coding RNAs that regulate gene expression in key biological processes such as proliferation, apoptosis, invasion, and metastasis [ 16 , 17 , 18 ] and have recently emerged as regulators of the complex mechanisms that drive BC therapeutic resistance or sensitivity. Extracellular vesicles (EVs) are small lipid bilayer-encapsulated vesicles that are released by living cells in the microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Circulating Small EVs miRNAs as Predictors of Pathological Response to Neo-Adjuvant Therapy in Breast Cancer Patients

Baldasici

Bălăcescu

Cruceriu

et al. 2022

IJMS

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Neo-adjuvant therapy (NAT) is increasingly used in the clinic for the treatment of breast cancer (BC). Pathological response to NAT has been associated with improved patients’ survival; however, the current techniques employed for assessing the tumor response have significant limitations. Small EVs (sEVs)-encapsulated miRNAs have emerged as promising new biomarkers for diagnosis and prediction. Therefore, our study aims to explore the predictive value of these miRNAs for the pathological response to NAT in BC. By employing bioinformatic tools, we selected a set of miRNAs and evaluated their expression in plasma sEVs and BC biopsies. Twelve miRNAs were identified in sEVs, of which, miR-21-5p, 221-3p, 146a-5p and 26a-5p were significantly associated with the Miller–Payne (MP) pathological response to NAT. Moreover, miR-21-5p, 146a-5p, 26a-5p and miR-24-3p were independent as predictors of MP response to NAT. However, the expression of these miRNAs showed no correlation between sEVs and tissue samples, indicating that the mechanisms of miRNA sorting into sEVs still needs to be elucidated. Functional analysis of miRNA target genes and drug interactions revealed that candidate miRNAs and their targets, can be regulated by different NAT regimens. This evidence supports their role in governing the patients’ therapy response and highlights their potential use as prediction biomarkers.

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MicroRNA-139, an Emerging Gate-Keeper in Various Types of Cancer

Cited by 6 publications

References 126 publications

Lifestyle-Driven Variations in Nutrimiromic MicroRNA Expression Patterns across and beyond Genders

Lifestyle-Driven Variations in Nutrimiromic MicroRNA Expression Patterns across and beyond Genders

Aberrant activation of Wnt/β-Catenin signaling pathway drives the expression of poor prognosis-associated microRNAs in adrenocortical cancer with a major impact on miR-139-5p and its host gene PDE2A

Circulating Small EVs miRNAs as Predictors of Pathological Response to Neo-Adjuvant Therapy in Breast Cancer Patients

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