Impact of somatic copy number alterations on the glioblastoma mi<scp>RN</scp>ome: miR‐4484 is a genomically deleted tumour suppressor

Nawaz, Zahid; Patil, Vikas; Thinagararjan, Sivaarumugam; Rao, Soumya; Hegde, Anupama; Arivazhagan, Arimappamagan; Santosh, Vani; Somasundaram, Kumaravel

doi:10.1002/1878-0261.12060

Cited by 23 publications

(16 citation statements)

References 35 publications

(57 reference statements)

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“…Although studies have investigated the relationship between miRNAs and SCNAs, most were focused on specific miRNAs, SCNAs of specific genes, or a single cancer type [9,10,11,12,13,14,15,16]. The genome-wide association between miRNA expression and SCNAs across several cancer types has not been widely investigated.…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer

Soh

Cho

Choi

et al. 2018

Cancers

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MicroRNAs (miRNAs) are key molecules that regulate biological processes such as cell proliferation, differentiation, and apoptosis in cancer. Somatic copy number alterations (SCNAs) are common genetic mutations that play essential roles in cancer development. Here, we investigated the association between miRNAs and SCNAs in cancer. We collected 2538 tumor samples for seven cancer types from The Cancer Genome Atlas. We found that 32−84% of miRNAs are in SCNA regions, with the rate depending on the cancer type. In these regions, we identified 80 SCNA-miRNAs whose expression was mainly associated with SCNAs in at least one cancer type and showed that these SCNA-miRNAs are related to cancer by survival analysis and literature searching. We also identified 58 SCNA-miRNAs common in the seven cancer types (CC-SCNA-miRNAs) and showed that these CC-SCNA-miRNAs are more likely to be related with protein and gene expression than other miRNAs. Furthermore, we experimentally validated the oncogenic role of miR-589. In conclusion, our results suggest that SCNA-miRNAs significantly alter biological processes related to cancer development, confirming the importance of SCNAs in non-coding regions in cancer.

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Section: Introductionmentioning

confidence: 99%

Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer

Soh

Cho

Choi

et al. 2018

Cancers

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“…Maybe these miRNAs do not be expressed in the mitochondria of spermatozoa, or their expression is very low. The miR‐4484 has been showed a putative marker in lymphoma (Tamaddon, Geramizadeh, Karimi, Mowla, & Abroun, ), glioblastoma (Nawaz et al, ), cervical squamous cell carcinoma (Chen et al, ) and breast cancer (Tamaddon et al, ) and in occupational noise‐induced hearing loss (Li et al, ). Previous studies showed the role of miR‐4463 overexpression in inhibiting aberrant vascular smooth muscle cell (VSMC) migration(Wang et al, ), enhancing H 2 O 2 induced oxidative stress and apoptosis (Wang, He, Deng, He, & Zhou, ), novel biomarker in arteriosclerosis obliterans (He et al, ) and polycystic ovary syndrome (Ding et al, ).…”

Section: Discussionmentioning

confidence: 99%

MiR‐4485‐3p expression reduced in spermatozoa of men with idiopathic asthenozoospermia

et al. 2020

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Asthenozoospermia (AZS), which characterised by reduced forward sperm motility, is a common cause of male infertility. Recently, mitochondrial dysfunction reported in AZS men came to attention for finding the molecular aetiology of AZS. Mitochondria‐related microRNAs (miRNAs) are the most important regulators of mitochondrial function through post‐transcriptionally modulation of gene expression. Therefore, this study aims to evaluate the expression of four recently reported mitochondrial‐related miRNAs (miR‐4485‐3p/4484/4461 and 4463) in the sperm sample of asthenozoospermic men. RNA was extracted from spermatozoa of 74 volunteers (39 patients with idiopathic AZS and 35 controls with normal fertility), and relative gene expression analysis was performed by quantitative PCR. We used SNORD48 as a normaliser gene, and quantification was calculated by 2−ΔΔCt method. The expression of miR‐4484 and miR‐4461 was not detected in the spermatozoa of cases and controls. However, miR‐4485‐3p (p = .006) was significantly downregulated in the AZS men compared with the controls, but the miR‐4463 expression was not significantly different between the two groups (p = .5). Bioinformatic analysis identified three target genes for miR‐4485‐3p (DNAH1, KIT and PARK7) that are related to male infertility. In conclusion, the downregulation of miR‐4485‐3p was associated with idiopathic AZS, which could be a molecular link between mitochondrial dysfunction and AZS.

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“…It is located at chromosome 10q26.2, and it contains 83 bases. Up to now, the expression of miR-4484 has been evaluated in several types of cancer, such as breast cancer 15 , glioblastoma 16 , diffuse large B-cell lymphoma 17 , as well as oral lichen planus 18 . Interestingly, there is only one study, by Christmann et al .…”

Section: Discussionmentioning

confidence: 99%

“…Although MMP-21 is not predicted to be a target of miR-4484 by bioinformatics programs described above, it has attracted our attention since miR-4484, and MMP-21 genes are located in the immediate vicinity on chromosome 10, and MMP-21 has not been evaluated in SSc yet. miR-4484 is an intragenic miRNA that resides in the first intron of the uroporphyrinogen III synthetase (UROS) gene and MMP-21 resides downstream to UROS (at the distance of ~13 kb) 16 . Based on this data, it is tempting to speculate whether there exists any inter-relationship between the expression of miR-4484 and MMP-21 16 .…”

Section: Discussionmentioning

confidence: 99%

A novel miRNA-4484 is up-regulated on microarray and associated with increased MMP-21 expression in serum of systemic sclerosis patients

Rusek

Michalska-Jakubus

Kowal

et al. 2019

Sci Rep

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Systemic sclerosis (SSc) is a complex, heterogeneous connective tissue disease, characterized by fibrosis and ECM deposition in skin and internal organs, autoimmunity, and changes in the microvasculature. Profiling of circulating miRNAs in serum has been found to be changed in pathological states, creating new possibilities for molecular diagnostics as blood-based biomarkers. This study was designed to identify miRNAs that are differentially expressed in SSc and might be potentially contributing to the disease etiopathogenesis or be used for diagnostic purposes. Thus, we compared the expression pattern of multiple miRNAs in serum of 10 SSc patients to 6 healthy controls using microarray analysis, and RT-qPCR to confirm the obtained results. In addition, bioinformatics analysis was performed to explore miRNAs target genes and the signaling pathways that may be potentially involved in SSc pathogenesis. Our study shows a different expression of 15 miRNAs in SSc patients. We identified that miR-4484, located on chromosome 10q26.2, was an 18-fold up-regulated in SSc patients compared to a control group. Bioinformatics analysis of the miR-4484 target genes and the signaling pathways showed that it might be potentially involved in the TGF-β signaling pathway, ECM-receptor interaction, and metalloproteinases expression. Based on the chromosomal location, the most interesting target gene of miR-4484 may be MMP-21. We found that the expression of MMP-21 significantly increased in SSc patients compared to healthy subjects (P < 0.05). Our results suggest that miR-4484, and MMP-21 might be novel serum biomarkers that may correspond to pathological fibrosis in SSc, but it needs to be validated in further studies.

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Impact of somatic copy number alterations on the glioblastoma miRNome: miR‐4484 is a genomically deleted tumour suppressor

Cited by 23 publications

References 35 publications

Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer

Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer

MiR‐4485‐3p expression reduced in spermatozoa of men with idiopathic asthenozoospermia

A novel miRNA-4484 is up-regulated on microarray and associated with increased MMP-21 expression in serum of systemic sclerosis patients

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