Identification of the transcriptional promoters in the proximal regions of human microRNA genes

Long, Yue-Sheng; Deng, Guangbing; Sun, Xunsha; Yi, Yong‐Hong; Su, Tao; Zhao, Qi‐Hua; Liao, Wei‐Ping

doi:10.1007/s11033-010-0535-y

Cited by 16 publications

(22 citation statements)

References 23 publications

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“…[6][7][8][9] This hypothesis is supported by recent research predicting miRNA promoters by combining bioinformatic analysis of nearby upstream DNA regulatory elements (transcription start sites (TSS), conserved transcription factor-binding sites, TATA boxes, A/B boxes) and epigenetic modifications (CpG islands, histone modifications, nucleosome positioning patterns) with chromatin immunopreciptiation screens or reporter assays. [6][7][8][9][10][11] It seems that about half of the miRNAs located in introns of protein-coding genes (B60%) contain putative promoters regulating transcription independent of their host gene. 7 This is also supported by the observed discrepancy in expression of several miRNAs and their host genes.…”

Section: Genomic Organization Of the Mir-125b Clustermentioning

confidence: 97%

“…Hsa-let-7a-2 Hsa-miR-125b-1 A putative promoter predicted by Long et al, 7 Wang et al, 9 Ozsolak et al 8 and Corcoran et al 6 2: A putative promoter predicted by Long et al, 7 Wang et al, 9 and Corcoran et al 6 3: A putative promoter predicted by Long et al, 7 Wang et al, 9 Ozsolak et al, 8 Corcoran et al, 6 and Montey et al…”

Section: Hsa-mir-100mentioning

confidence: 99%

“…[6][7][8][9][10][11] It seems that about half of the miRNAs located in introns of protein-coding genes (B60%) contain putative promoters regulating transcription independent of their host gene. 7 This is also supported by the observed discrepancy in expression of several miRNAs and their host genes. 12,13 Ozsolak et al 8 showed that intronic miRNAs having independent transcription initiation regions had the shortest TSS-to-miRNA distance with a mean distance of 4.2±3.5 kb.…”

Section: Genomic Organization Of the Mir-125b Clustermentioning

confidence: 99%

“…Several independent putative promoters have been described (Figure 1b). One that drives co-expression of hsa-miR-100 and hsa-let-7a-2 independent of their potential host gene, [6][7][8][9] one that drives co-expression of hsa-miR-99a and hsa-let-7c independent of their host gene, [6][7][8][9]11 and another that drives co-expression of hsa-miR-99b, hsa-let-7c and hsa-miR-125a.…”

Section: Genomic Organization Of the Mir-125b Clustermentioning

confidence: 99%

“…4: A putative promoter predicted by Corcoran et al, 6 and Ozsolak et al 8 5: A putative promoter predicted by Long et al, 7 Wang et al, 9 Ozsolak et al, 8 and Corcoran et al 6 Dashed lines indicate structures that were annotated only in a single study.…”

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confidence: 99%

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MiR-125 in normal and malignant hematopoiesis

et al. 2012

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MiR-125 is a highly conserved microRNA throughout many different species from nematode to humans. In humans, there are three homologs (hsa-miR-125b-1, hsa-miR-125b-2 and hsa-miR-125a). Here we review a recent research on the role of miR-125 in normal and malignant hematopoietic cells. Its high expression in hematopoietic stem cells (HSCs) enhances self-renewal and survival. Its expression in specific subtypes of myeloid and lymphoid leukemias provides resistance to apoptosis and blocks further differentiation. A direct oncogenic role in the hematopoietic system has recently been demonstrated by several mouse models. Targets of miR-125b include key proteins regulating apoptosis, innate immunity, inflammation and hematopoietic differentiation.

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Section: Genomic Organization Of the Mir-125b Clustermentioning

confidence: 97%

Section: Hsa-mir-100mentioning

confidence: 99%

Section: Genomic Organization Of the Mir-125b Clustermentioning

confidence: 99%

Section: Genomic Organization Of the Mir-125b Clustermentioning

confidence: 99%

mentioning

confidence: 99%

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MiR-125 in normal and malignant hematopoiesis

et al. 2012

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A p53‐Dependent Tumor Suppressor Network Is Induced by Selective miR‐125a‐5p Inhibition in Multiple Myeloma Cells

Leotta

Biamonte

Raimondi

et al. 2014

Journal Cellular Physiology

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The analysis of deregulated microRNAs (miRNAs) is emerging as a novel approach to disclose the regulation of tumor suppressor or tumor promoting pathways in tumor cells. Targeting aberrantly expressed miRNAs is therefore a promising strategy for cancer treatment. By miRNA profiling of primary plasma cells from multiple myeloma (MM) patients, we previously reported increased miR-125a-5p levels associated to specific molecular subgroups. On these premises, we aimed at investigating the biological effects triggered by miR-125a-5p modulation in MM cells. Expression of p53 pathway-related genes was down-regulated in MM cells transfected with miR-125a-5p mimics. Luciferase reporter assays confirmed specific p53 targeting at 3 0 UTR level by miR-125a-5p mimics. Interestingly, bone marrow stromal cells (BMSCs) affected the miR-125a-5p/p53 axis, since adhesion of MM cells to BMSCs strongly up-regulated miR-125a-5p levels, while reduced p53 expression. Moreover, ectopic miR-125a-5p reduced, while miR-125-5p inhibitors promoted, the expression of tumor suppressor miR-192 and miR-194, transcriptionally regulated by p53. Lentiviral-mediated stable inhibition of miR-125a-5p expression in wild-type p53 MM cells dampened cell growth, increased apoptosis and reduced cell migration. Importantly, inhibition of in vitro MM cell proliferation and migration was also achieved by synthetic miR-125a-5p inhibitors and was potentiated by the co-expression of miR-192 or miR-194. Taken together, our data indicate that miR-125a-5p antagonism results in the activation of p53 pathway in MM cells, underlying the crucial role of this miRNA in the biopathology of MM and providing the molecular rationale for the combinatory use of miR-125a inhibitors and miR-192 or miR-194 mimics for MM treatment.

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DNA methylation regulated microRNAs in human cervical cancer

Varghese

Shukla

Kabekkodu

et al. 2017

Molecular Carcinogenesis

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Regulation of miRNA gene expression by DNA promoter methylation may represent a key mechanism to drive cervical cancer progression. In order to understand the impact of DNA promoter methylation on miRNAs at various stages of cervical carcinogenesis, we performed DNA methylation microarray on Normal Cervical Epithelium (NCE), Cervical Intraepithelial Neoplasia (CIN I-III) and Squamous Cell Carcinoma (SCC) tissues to identify differentially methylated miRNAs followed by validation by bisulfite sequencing. Further, expression of miRNAs was analyzed by qRT-PCR in clinical tissues and cervical cancer cell lines. Transcriptional activity was determined by luciferase assay. We identified a total of 69 hypermethylated and hypomethylated miRNA promoters encompassing 78 CpG islands in all except Y chromosome, among the three groups. The candidate DNA promoters of miR-424 were significantly hypermethylated and miR-200b and miR-34c were significantly hypomethylated in SCC compared to NCE (P < 0.05). Expression of miR-424, miR-200b, and miR-34c were inversely correlated with promoter DNA methylation in tissue samples. Treatment of cell lines with 5-aza-2'-deoxycytidine showed differential expression in all three miRNAs. We observed a decrease in miRNA promoter activity following in vitro SssI methylase treatment of miR-424, miR-200b, and miR-34c. Luciferase assay demonstrated that miR-200b and miR-424 functionally interacts with 3'-UTR of HIPK3 and RBBP6 respectively and decreased their activity in presence of miR-200b and miR-424 mimics transfected in SiHa cells. Taken together, we have identified deregulation of miRNAs by aberrant DNA promoter methylation, leading to its transcriptional silencing during cervical carcinogenesis, which can be potential targets for diagnosis and therapy.

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Identification of the transcriptional promoters in the proximal regions of human microRNA genes

Cited by 16 publications

References 23 publications

MiR-125 in normal and malignant hematopoiesis

MiR-125 in normal and malignant hematopoiesis

A p53‐Dependent Tumor Suppressor Network Is Induced by Selective miR‐125a‐5p Inhibition in Multiple Myeloma Cells

DNA methylation regulated microRNAs in human cervical cancer

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