Integrated copy number and miRNA expression analysis in triple negative breast cancer of Latin American patients

Sugita, Bruna M.; Pereira, Silma Regina Ferreira; Almeida, Rodrigo Coutinho de; Gill, Mandeep; Mahajan, Akanksha; Duttargi, Anju; Kirolikar, Saurabh; Fadda, Paolo; Lima, Rubens Silveira de; Úrban, Cícero; Makambi, Kepher H.; Madhavan, Subha; Boca, Simina M.; Gusev, Yuriy; Cavalli, Iglenir João; Ribeiro, Enilze M.S.F.; Cavalli, Luciane R.

doi:10.18632/oncotarget.27250

Cited by 18 publications

(27 citation statements)

References 119 publications

(119 reference statements)

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“…The genes affected in the R337H+ group were located in the cytobands, which were mainly affected by CNAs in these cases, such as 1q21.2, 1q44, 2q13, 2q31.1, 2q32.2, 2q35, 8q21.3, 8q22.3, 8q23.1, 16q23.2, and 17q25.3 (in the R337H− group, only genes mapped at 8q were observed in this integration analysis). Although the impact of such alterations in gene and miRNA expression has to be confirmed in experimental expression assays, the observations support the finding that CNAs can affect genes that are also potentially regulated by miRNAs 33 , 34 , 41 – 44 . Several of these genes were previously identified as members of the main signaling pathways observed and, interestingly, displayed direct protein interactions with p53 (data not shown—String Network v. 11.0 ( https://string-db.org/ ).…”

Section: Discussionsupporting

confidence: 57%

“…For the selection of the main targets, only those that presented strong evidence in validation methods (luciferase assays, western blotting, and qPCR) were considered, according to miRTarBase v.7.0 28 . A direct integration of the miRNA target genes mapped in the most affected cytobands was performed, as previously described 42,44 to determine whether the genes also mapped in these regions were miRNA targets, and therefore could be potentially affected by both CNAs and miRNA expression regulation.…”

Section: Functional Enriched Pathways For Both Groups Of Breast Cancmentioning

confidence: 99%

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Frequency of the TP53 R337H variant in sporadic breast cancer and its impact on genomic instability

Mathias

Bortoletto²,

Centa³

et al. 2020

Sci Rep

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The R337H is a TP53 germline pathogenic variant that has been associated with several types of cancers, including breast cancer. Our main objective was to determine the frequency of the R337H variant in sporadic breast cancer patients from Paraná state, South Brazil, its association with prognosis and its impact in genomic instability. The genotyping of 805 breast cancer tissues revealed a genotypic and allelic frequency of the R337H variant of 2.36% and 1.18%, respectively. In these R337H+ cases a lower mean age at diagnosis was observed when compared to the R337H-cases. Array-CGH analysis showed that R337H+ patients presented a higher number of copy number alterations (CNAs), compared to the R337H−. These CNAs affected genes and miRNAs that regulate critical cancer signaling pathways; a number of these genes were associated with survival after querying the KMplot database. Furthermore, homozygous (R337H+/R337H+) fibroblasts presented increased levels of copy number variants when compared to heterozygous or R337H− cells. In conclusion, the R337H variant may contribute to 2.36% of the breast cancer cases without family cancer history in Paraná. Among other mechanisms, R337H increases the level of genomic instability, as evidenced by a higher number of CNAs in the R337H+ cases compared to the R337H−.

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Section: Discussionsupporting

confidence: 57%

Section: Functional Enriched Pathways For Both Groups Of Breast Cancmentioning

confidence: 99%

Frequency of the TP53 R337H variant in sporadic breast cancer and its impact on genomic instability

Mathias

Bortoletto²,

Centa³

et al. 2020

Sci Rep

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“…RNA was isolated from the 10-μm sections of the lung tissue biopsies from the Control and COVID-19 groups as previously described ( 23 , 24 ). RNA was reverse transcribed and amplified by RT-quantitative PCR (qPCR) using TaqMan probes for miR-26a-5p (assay number 000405), miR-29b-3p (assay number 000413), and miR-34a-5p (assay number 000426), and RNU48 (assay number 1006) (normalizer) (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients

Centa

Fonseca

Ferreira

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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MicroRNAs (miRNAs) are critical modulators of endothelial homeostasis, which highlights their involvement in vascular diseases, including the ones caused by virus infections. Our main objective was to identify miRNAs involved in the endothelial function and determine their expression in post-mortem lung biopsies of COVID-19 patients with severe respiratory injuries and thrombotic events. Based on functional enrichment analysis, miR-26a-5p, miR-29b-3p, and miR-34a-5p were identified as regulators of mRNA targets involved in endothelial, and inflammatory signaling pathways as well as in viral diseases. A miRNA/mRNA network, constructed based on protein-protein interactions of the miRNA targets and the inflammatory biomarkers characterized in the patients, revealed a close interconnection of these miRNAs with relevance to the endothelial activation/dysfunction. Reduced expression levels of selected miRNAs were observed in the lung biopsies of COVID-19 patients (n=9) compared to the Controls (n=10)(P<0.01-0.0001). MiR-26a-5p and miR-29b-3p presented the best power to discriminate these groups (AUC=0.8286, and AUC=0.8125, respectively). The correlation analysis of the miRNAs with inflammatory biomarkers in the COVID-19 patients was significant for miR-26a-5p [IL-6 (r2=0.5414), and ICAM-1(r2=0.5624)], and miR-29b-3p [IL-4 (r2=0.8332), and IL-8 (r2=0.2654)]. Altogether, these findings demonstrate the relevance and the non-random involvement of miR-26a-5p, miR-29b-3p, and miR-34a-5p in endothelial dysfunction and inflammatory response in patients with SARS-CoV-2 infection and the occurrence of severe lung injury and immunothrombosis.

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“…Robust miR-1260a/1260b expression in maternal breast milk may impart immune protection on the infant gut [ 56 ]. Expression of miR-1260a has been described as bring downregulated in TNBC tissue [ 57 ] and high levels of miR-1260a in the serum of metastatic BC patients is associated with a poor prognosis [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Pathway Analysis of Selected Circulating miRNAs in Plasma of Breast Cancer Patients: A Preliminary Study

Holubeková

Kolková

Grendár

et al. 2020

IJMS

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MicroRNAs in the circulation of breast cancer (BC) patients have great potential for the early diagnosis, treatment and monitoring of breast cancer. The aim of this preliminary study was to obtain the expression profile of selected miRNAs in the plasma of BC patients that could discriminate BC patients from healthy volunteers and may be useful in early detection of BC. Significantly deregulated miRNAs were evaluated by pathway analysis with the prediction of potential miRNA targets. The study enrolled plasma samples from 65 BC patients and 34 healthy volunteers. Selected miRNAs were screened in pilot testing by the real-time PCR (qPCR) method, and the most appropriate reference genes were selected for normalisation by the geNorm algorithm. In the final testing, we detected miR-99a, miR-130a, miR-484 and miR-1260a (p < 0.05) as significantly up-regulated in the plasma of BC patients. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis revealed that all significantly deregulated miRNAs are involved in the Hippo and Transforming Growth Factor-beta (TGF-beta) signalling pathways. Our study confirmed a different profile of selected circulating miRNAs in the plasma of BC patients with an emphasis on some critical points in the analysis process.

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Integrated copy number and miRNA expression analysis in triple negative breast cancer of Latin American patients

Cited by 18 publications

References 119 publications

Frequency of the TP53 R337H variant in sporadic breast cancer and its impact on genomic instability

Frequency of the TP53 R337H variant in sporadic breast cancer and its impact on genomic instability

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients

Pathway Analysis of Selected Circulating miRNAs in Plasma of Breast Cancer Patients: A Preliminary Study

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