Diagnostic and prognostic potential clustered miRNAs in bladder cancer

Ware, Akshay P.; Kabekkodu, Shama Prasada; Chawla, Arun; Paul, Babu Sena; Satyamoorthy, Kapaettu

doi:10.1007/s13205-022-03225-z

Cited by 9 publications

(9 citation statements)

References 69 publications

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“…Moreover, the DNA methylation status at the CpG site region approximately 17.6 kb upstream was reported to be critical in C19MC regulation (Tsai et al 2009 ). In our previous study (Ware et al 2022b ), we found that C19MC was upregulated and co-localized with RCNV in BCa. Further investigation revealed that C19MC member expression was not statistically significant in patient survival analyses.…”

Section: Discussionmentioning

confidence: 59%

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: Discussionmentioning

confidence: 59%

Integrated multiomics analysis of chromosome 19 miRNA cluster in bladder cancer

Ware,

Satyamoorthy,

Paul

2023

Funct Integr Genomics

Self Cite

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“…It is also noteworthy that most studies classified BC patients based on the expression level of the analyzed miRNAs, which is useful when addressing their implications. The most reported miRNAs in the different studies were miR-141 and -200, which were both members of the miR200 family in seven studies [39,41,51,62,63,65,68]; and according to the results, a high expression of these molecules was correlated with higher overall survival [39,51,62,65,68] and lower MIBC incidence [63]. Interestingly, these studies were performed on tumor tissue samples, while the only study using liquid biopsies showed that increased urine miR-200a levels were correlated with high-risk BC [41]; this could be explained by methodological variability amongst the studies.…”

Section: Mirnas As Prognostic Tools In Bcmentioning

confidence: 99%

“…Lastly, the members of the miR200 family (miR-200a, -200b, -200c, -141, and -429) were the most analyzed in the reviewed studies [39,41,51,62,63,65,68]. These miRNAs have been described as tumor suppressors in some cancers.…”

Section: Biological Plausibility Of Described Mirnas In Bcmentioning

confidence: 99%

The Role of miRNAs to Detect Progression, Stratify, and Predict Relevant Clinical Outcomes in Bladder Cancer

Torres-Bustamante,

Vazquez-Urrutia,

Solorzano-Ibarra

et al. 2024

IJMS

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Bladder cancer (BC) is one of the most common types of cancer worldwide, with significant differences in survival depending on the degree of muscle and surrounding tissue invasion. For this reason, the timely detection and monitoring of the disease are important. Surveillance cystoscopy is an invasive, costly, and uncomfortable procedure to monitor BC, raising the need for new, less invasive alternatives. In this scenario, microRNAs (miRNAs) represent attractive prognostic tools given their role as gene regulators in different biological processes, tissue expression, and their ease of evaluation in liquid samples. In cancer, miRNA expression is dynamically modified depending on the tumor type and cancer staging, making them potential biomarkers. This review describes the most recent studies in the last five years exploring the utility of miRNA-based strategies to monitor progression, stratify, and predict relevant clinical outcomes of bladder cancer. Several studies have shown that multimarker miRNA models can better predict overall survival, recurrence, and progression in BC patients than traditional strategies, especially when combining miRNA expression with clinicopathological variables. Future studies should focus on validating their use in different cohorts and liquid samples.

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“…It is well documented that miRNAs are involved in the regulation of all biological processes [51,52] , and a large body of research has demonstrated that the deregulation of miRNA expression is associated with the initiation, development, and metastatic dissemination of human tumor cells [53][54][55][56][57][58] . Recent studies have also shown that miRNA profiles of tumor cells can provide both diagnostic and prognostic information on tumor progression [59][60][61][62] . Importantly, tumor cells can exchange miRNAs with both neighboring and distant cells via EVs.…”

Section: Introductionmentioning

confidence: 99%

Non-invasive detection of orthotopic human lung tumors by microRNA expression profiling of mouse exhaled breath condensates and exhaled extracellular vesicles

Mitchell,

Ben-Dov,

Liu

et al. 2024

Extracell Vesicles Circ Nucleic Acids

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Aim: The lung is the second most frequent site of metastatic dissemination. Early detection is key to improving survival. Given that the lung interfaces with the external environment, the collection of exhaled breath condensate (EBC) provides the opportunity to obtain biological material including exhaled miRNAs that originate from the lung. Methods: In this proof-of-principal study, we used the highly metastatic MDA-MB-231 subline 3475 breast cancer cell line (LM-3475) to establish an orthotopic lung tumor-bearing mouse model and investigate non-invasive detection of lung tumors by analysis of exhaled miRNAs. We initially conducted miRNA NGS and qPCR validation analyses on condensates collected from unrestrained animals and identified significant miRNA expression differences between the condensates of lung tumor-bearing and control mice. To focus our purification of EBC and evaluate the origin of these differentially expressed miRNAs, we developed a system to collect EBC directly from the nose and mouth of our mice. Results: Using nanoparticle distribution analyses, TEM, and ONi super-resolution nanoimaging, we determined that human tumor EVs could be increasingly detected in mouse EBC during the progression of secondary lung tumors. Using our customizable EV-CATCHER assay, we purified human tumor EVs from mouse EBC and demonstrated that the bulk of differentially expressed exhaled miRNAs originate from lung tumors, which could be detected by qPCR within 1 to 2 weeks after tail vein injection of the metastatic cells. Conclusion: This study is the first of its kind and demonstrates that lung tumor EVs are exhaled in mice and provide non-invasive biomarkers for detection of lung tumors.

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Diagnostic and prognostic potential clustered miRNAs in bladder cancer

Cited by 9 publications

References 69 publications

Integrated multiomics analysis of chromosome 19 miRNA cluster in bladder cancer

Integrated multiomics analysis of chromosome 19 miRNA cluster in bladder cancer

The Role of miRNAs to Detect Progression, Stratify, and Predict Relevant Clinical Outcomes in Bladder Cancer

Non-invasive detection of orthotopic human lung tumors by microRNA expression profiling of mouse exhaled breath condensates and exhaled extracellular vesicles

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