The miR-503 cluster is coordinately under-expressed in endometrial endometrioid adenocarcinoma and targets many oncogenes, cell cycle genes, DNA repair genes and chemotherapy response genes

Devor, Eric J.; Cha, Elizabeth; Warrier, Akshaya; Miller, M.D.; Bosquet, Jesús González; Leslie, Kimberly K.

doi:10.2147/ott.s180921

Cited by 9 publications

(7 citation statements)

References 27 publications

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“…In both groups, the majority of microRNAs was up-regulated: 13 out of 16 microRNAs in the ZEN medium group, and 41 out of 67 microRNAs in the ZEN high group were increased compared to the Control group. The most prominent changes in the expression of individual microRNAs were observed in the ZEN high group, especially on the microRNAs from the miR-503 cluster 26 (miR-424-5p, miR-450a, miR-450b-5p, miR-450c-5p, miR-503, and miR-542-3p) with 6.0 to 12.6 fold increase.…”

Section: Resultsmentioning

confidence: 97%

“…By doing so, the initially large number of microRNA-mRNA interaction sites was narrowed down to the most likely target genes (Table 2). The prediction analysis for the five up-regulated microRNAs (known to belong to the same cluster miR-503 26 ) showed that 346 target genes were found at least in the prediction datasets of two of these microRNAs. Extra analysis on network prediction and interconnection of genes was done with miRNet and is included in Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In line with that, our target gene prediction analysis also identified ZNF217 as a major target for miR-503. This in silico prediction analysis was carried out with the five most up-regulated microRNAs (miR-424-5p, miR-450a, miR-450b-5p, miR-450c-5p, miR-503, and miR-542-3p) in the uterus of piglets fed ZEN, which have been recently reported to all belong to the aforementioned miR-503 cluster in humans, and linked to endometrial adenocarcinoma 26,39 . Due to large output in microRNA prediction analysis, the resulting list of target genes was further filtered excluding genes with low prediction scores and uncommon genes across microRNAs.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNAs in porcine uterus and serum are affected by zearalenone and represent a new target for mycotoxin biomarker discovery

Grenier¹,

Hackl²,

Skalicky³

et al. 2019

Sci Rep

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The mycotoxin zearalenone (ZEN) poses a risk to animal health because of its estrogenic effects. Diagnosis of ZEN-induced disorders remains challenging due to the lack of appropriate biomarkers. In this regard, circulating microRNAs (small non-coding RNAs) have remarkable potential, as they can serve as indicators for pathological processes in tissue. Thus, we combined untargeted and targeted transcriptomics approaches to investigate the effects of ZEN on the microRNA expression in porcine uterus, jejunum and serum, respectively. To this end, twenty-four piglets received uncontaminated feed (Control) or feed containing 0.17 mg/kg ZEN (ZEN low), 1.46 mg/kg ZEN (ZEN medium) and 4.58 mg/kg ZEN (ZEN high). After 28 days, the microRNA expression in the jejunum remained unaffected, while significant changes in the uterine microRNA profile were observed. Importantly, 14 microRNAs were commonly and dose-dependently affected in both the ZEN medium and ZEN high group, including microRNAs from the miR-503 cluster (i.e. ssc-miR-424-5p, ssc-miR-450a, ssc-miR-450b-5p, ssc-miR-450c-5p, ssc-miR-503 and ssc-miR-542-3p). Predicted target genes for those microRNAs are associated with regulation of gene expression and signal transduction (e.g. cell cycle). Although the effects in serum were less pronounced, receiver operating characteristic analysis revealed that several microRNA ratios were able to discriminate properly between non-exposed and ZEN-exposed pigs (e.g. ssc-miR-135a-5p/ssc-miR-432-5p, ssc-miR-542-3p/ssc-miR-493-3p). This work sheds new light on the molecular mechanisms of ZEN, and fosters biomarker discovery.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNAs in porcine uterus and serum are affected by zearalenone and represent a new target for mycotoxin biomarker discovery

Grenier¹,

Hackl²,

Skalicky³

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…For example, increased expression of miR-21 and miR-146b is related to loss of DNA methylation in papillary thyroid carcinoma 22 . miR-503 cluster is coordinately underexpressed in endometrial endometrioid adenocarcinoma and targets many oncogenes, cell cycle genes, DNA repair genes, and chemotherapy-response genes 23 . On the other hand, miRNA expression is also subjected to the epigenetic regulatory network during tumor progression 24 , which can be downregulated by DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

miR-148-3p Inhibits Growth of Glioblastoma Targeting DNA Methyltransferase-1 (DNMT1)

Chen

Chu

et al. 2019

oncol res

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To date, miR-148-3p and DNMT1‐recombinant human runt-related transcription factor 3 (RUNX3) axis have been linked to cell proliferation, migration, and invasion; however, their roles and relationships in human glioblastoma multiforme (GBM) are still not clear. Here we found that the expression of miR-148-3p in glioma tissues was decreased compared with adjacent nontumor tissues and correlated with WHO grade, tumor size, and prognosis as well as DNMT1 and RUNX3 expressions. Compared with NHA cells, the expression of miR-148-3p in U87 and U251 cells was also downregulated and accompanied with upregulation of DNMT1 and hypermethylation level of RUNX3 promoter region. miR-148-3p overexpression induced apoptosis and cell cycle arrest of U87 and U251 cells, and affected cell migration and invasion. miR-148-3p mimics effectively suppressed the expression of DNMT1 and methylation of RUNX3 promoter, finally upregulating RUNX3 expression. Mechanistically, the 3′-untranslated region (3′-UTR) of DNMT1 was a direct target of miR-148-3p. Overexpression of miR-148-3p or inhibition of DNMT1 induced the expression of E-cadherin and reduced the expressions of N-cadherin, vimentin, MMP-2, and MMP-9. In conclusion, miR-148-3p directly repressed the expression of DNMT1 and inhibited proliferation, migration, and invasion by regulating DNMT1‐RUNX3 axis and the epithelial‐mesenchymal transition in GBM. Our findings provide a new foundation for treatment of patients with GBM.

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“…Using 5-Aza-CdR, levels of this miRNA increased, which resulted in suppressed cell proliferation, migration, invasion, and EMT of PC cells [ 163 ]. MiR-424 also functions as an important tumor suppressor, and its expression is inversely correlated with promoter DNA methylation in GBM [ 164 ], CC [ 118 ], endometrial endometrioid adenocarcinoma [ 165 ], and OC [ 166 ].…”

Section: Epigenetic Regulation Of Microrna Clusters and Families Dmentioning

confidence: 99%

Epigenetic Regulation of MicroRNA Clusters and Families during Tumor Development

Gregorová

Vychytilova-Faltejskova

Ševčı́ková

2021

Cancers

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MicroRNAs are small non-coding single-stranded RNA molecules regulating gene expression on a posttranscriptional level based on the seed sequence similarity. They are frequently clustered; thus, they are either simultaneously transcribed into a single polycistronic transcript or they may be transcribed independently. Importantly, microRNA families that contain the same seed region and thus target related signaling proteins, may be localized in one or more clusters, which are in a close relationship. MicroRNAs are involved in basic physiological processes, and their deregulation is associated with the origin of various pathologies, including solid tumors or hematologic malignancies. Recently, the interplay between the expression of microRNA clusters and families and epigenetic machinery was described, indicating aberrant DNA methylation or histone modifications as major mechanisms responsible for microRNA deregulation during cancerogenesis. In this review, the most studied microRNA clusters and families affected by hyper- or hypomethylation as well as by histone modifications are presented with the focus on particular mechanisms. Finally, the diagnostic and prognostic potential of microRNA clusters and families is discussed together with technologies currently used for epigenetic-based cancer therapies.

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The miR-503 cluster is coordinately under-expressed in endometrial endometrioid adenocarcinoma and targets many oncogenes, cell cycle genes, DNA repair genes and chemotherapy response genes

Cited by 9 publications

References 27 publications

MicroRNAs in porcine uterus and serum are affected by zearalenone and represent a new target for mycotoxin biomarker discovery

MicroRNAs in porcine uterus and serum are affected by zearalenone and represent a new target for mycotoxin biomarker discovery

miR-148-3p Inhibits Growth of Glioblastoma Targeting DNA Methyltransferase-1 (DNMT1)

Epigenetic Regulation of MicroRNA Clusters and Families during Tumor Development

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