CmirC: an integrated database of clustered miRNAs co-localized with copy number variations in cancer

Ware, Akshay P.; Satyamoorthy, Kapaettu; Paul, Babu Sena

doi:10.1007/s10142-022-00909-w

Cited by 6 publications

(4 citation statements)

References 46 publications

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“…We executed CmiRClustFinder v2.0 (Ware et al 2022a ) pipeline to identify recurrent copy number variations (RCNVs) from BCa patient data. The genome coordinates of C19MC in BED file format were given as input to identify their co-localization with significant RCNV regions.…”

Section: Methodsmentioning

confidence: 99%

Integrated multiomics analysis of chromosome 19 miRNA cluster in bladder cancer

Ware,

Satyamoorthy,

Paul

2023

Funct Integr Genomics

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With 46 microRNAs (miRNAs) embedded tandemly over a distance of ~100 kb, chromosome 19 microRNA cluster (C19MC) is the largest miRNA cluster in the human genome. The C19MC is transcribed from a long noncoding genomic region and is usually expressed simultaneously at a higher level. Hence, we performed an integrative multiomics data analysis to examine C19MC regulation, expression patterns, and their impact on bladder cancer (BCa). We found that 43 members of C19MC were highly expressed in BCa. However, its co-localization with recurrent copy number variation (CNV) gain was not statistically significant to implicate its upregulation. It has been reported that C19MC expression is regulated by a well-established CpG island situated 17.6 kb upstream of the transcription start site, but we found that CpG probes at this island were hypomethylated, which was not statistically significant in the BCa cohort. In addition, the promoter region of C19MC is strongly regulated by a group of seven transcription factors (NR2F6, SREBF1, TBP, GATA3, GABPB1, ETV4, and ZNF444) and five chromatin modifiers (SMC3, KDMA1, EZH2, RAD21, and CHD7). Interestingly, these 12 genes were found to be overexpressed in BCa patients. Further, C19MC targeted 42 tumor suppressor (TS) genes that were downregulated, of which 15 were significantly correlated with patient survival. Our findings suggest that transcription factors and chromatin modifiers at the promoter region may regulate C19MC overexpression. The upregulated C19MC members, transcription regulators, and TS genes can be further exploited as potential diagnostic and prognostic indicators as well as for therapeutic management of BCa.

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Section: Methodsmentioning

confidence: 99%

Integrated multiomics analysis of chromosome 19 miRNA cluster in bladder cancer

Ware,

Satyamoorthy,

Paul

2023

Funct Integr Genomics

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“…The non‐coding portions of the genome may exert important biological functions and control the gene expression involved in cancer 14 . MicroRNAs (miRNAs) are a class of small non‐coding RNA, about 19–25 nucleotides long, with the potential to regulate up to two‐thirds of all known human genes, at the post‐transcriptional level 15 .…”

Section: Introductionmentioning

confidence: 99%

“…13 The non-coding portions of the genome may exert important biological functions and control the gene expression involved in cancer. 14 MicroRNAs (miRNAs) are a class of small non-coding RNA, about 19-25 nucleotides long, with the potential to regulate up to two-thirds of all known human genes, at the post-transcriptional level. 15 Emerging evidence indicates that miRNAs play significant roles in key biological processes as well as in oncogenic mechanisms, including cell division, differentiation, development, invasion, migration, proliferation, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA copy number alterations in the malignant transformation of pleomorphic adenoma to carcinoma ex pleomorphic adenoma

Kimura,

Scarini,

Lavareze

et al. 2024

Head & Neck

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ObjectiveThis study used array comparative genomic hybridization to assess copy number alterations (CNAs) involving miRNA genes in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA), residual PA, and carcinoma ex pleomorphic adenoma (CXPA).Materials and MethodsWe analyzed 13 PA, 4 RPA, 29 CXPA, and 14 residual PA using Nexus Copy Number Discovery software. The miRNAs genes affected by CNAs were evaluated based on their expression patterns and subjected to pathway enrichment analysis.ResultsAcross the groups, we found 216 CNAs affecting 2261 miRNA genes, with 117 in PA, 59 in RPA, 846 in residual PA, and 2555 in CXPA. The chromosome 8 showed higher involvement in altered miRNAs in PAs and CXPA patients. Six miRNA genes were shared among all groups. Additionally, miR‐21, miR‐455‐3p, miR‐140, miR‐320a, miR‐383, miR‐598, and miR‐486 were prominent CNAs found and is implicated in carcinogenesis of several malignant tumors. These miRNAs regulate critical signaling pathways such as aerobic glycolysis, fatty acid biosynthesis, and cancer‐related pathways.ConclusionThis study was the first to explore CNAs in miRNA‐encoding genes in the PA‐CXPA sequence. The findings suggest the involvement of numerous miRNA genes in CXPA development and progression by regulating oncogenic signaling pathways.

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“…reported a decrease in the expression of CHD7 in testicular tissue in boys with high infertility risk, which was defined by decreased spermatogonia 2 . Additionally, overexpression of CHD7 in bladder cancer 3 or mutation in the CHD7 gene in colorectal cancer 4 has been reported, which suggests a hypothetical role of CHD7 on carcinogenesis. Thus, the direct effect of dysfunction of CHD7 in the testicular tissue should be considered.…”

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confidence: 99%

Editorial Comment to CHARGE syndrome with both primary and secondary hypogonadism

Iwatsuki,

Umemoto,

Yasui

2024

IJU Case Reports

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of spermatogenesis, GCNIS, or testicular germ cell cancer. 6 Actually, the present case was also complicated by maturation arrest of spermatogenesis and GCNIS. Skakkebaek et al. proposed the concept of TDS, 7 referring to a series of syndromes in which Leydig cell dysfunction caused by environmental factors during the fetal period leads to decreased testosterone secretion and abnormalities in sex differentiation such as hypogonadism and cryptorchidism. The causes of TDS might be environmental and/or genetic factors during the fetal period. 7 Although risk factors related to testicular dysfunction were not investigated in this case, we speculated that some factors during the fetal period might have caused maturation arrest of spermatogenesis, GCNIS, decreased steroid synthesis, and cryptorchidism. It is possible that GCNIS could have been prevented if surgery for non-palpable testes had been performed a little earlier.In conclusion, we have provided here the first report of CHARGE syndrome with both primary and secondary hypogonadism which was endocrinologically and histologically demonstrated. Immunohistochemistry also suggested GCNIS and loss of testosterone production. TDS caused by the action of environmental and/or genetic factors during the fetal period might exist in the background of this case. Registry and Registration No. of the study/trialNone.

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CmirC: an integrated database of clustered miRNAs co-localized with copy number variations in cancer

Cited by 6 publications

References 46 publications

Integrated multiomics analysis of chromosome 19 miRNA cluster in bladder cancer

Integrated multiomics analysis of chromosome 19 miRNA cluster in bladder cancer

MicroRNA copy number alterations in the malignant transformation of pleomorphic adenoma to carcinoma ex pleomorphic adenoma

Editorial Comment to CHARGE syndrome with both primary and secondary hypogonadism

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