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Article

miR-205-5p Downregulation and ZEB1 Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer

by
Lenka Kalinkova
1,†,
Nataliia Nikolaieva
1,†,
Bozena Smolkova
2,
Sona Ciernikova
1,
Karol Kajo
1,3,
Vladimir Bella
4,
Viera Horvathova Kajabova
2,
Helena Kosnacova
1,
Gabriel Minarik
5 and
Ivana Fridrichova
1,*
1
Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia
2
Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, Slovakia
3
Department of Pathology, St. Elisabeth Cancer Institute, 81250 Bratislava, Slovakia
4
Department of Senology, St. Elisabeth Cancer Institute, 81250 Bratislava, Slovakia
5
Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2022, 23(1), 103; https://doi.org/10.3390/ijms23010103
Submission received: 30 November 2021 / Revised: 20 December 2021 / Accepted: 21 December 2021 / Published: 22 December 2021
(This article belongs to the Special Issue Genetic and Epigenetic Regulations of Tumor Progression and Metastasis)
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Abstract

Background: Dissemination of breast cancer (BC) cells through the hematogenous or lymphogenous vessels leads to metastatic disease in one-third of BC patients. Therefore, we investigated the new prognostic features for invasion and metastasis. Methods: We evaluated the expression of miRNAs and epithelial-to-mesenchymal transition (EMT) genes in relation to CDH1/E-cadherin changes in samples from 31 patients with invasive ductal BC including tumor centrum (TU-C), tumor invasive front (TU-IF), lymph node metastasis (LNM), and CD45-depleted blood (CD45-DB). Expression of miRNA and mRNA was quantified by RT-PCR arrays and associations with clinico-pathological characteristics were statistically evaluated by univariate and multivariate analysis. Results: We did not verify CDH1 regulating associations previously described in cell lines. However, we did detect extremely high ZEB1 expression in LNMs from patients with distant metastasis, but without regulation by miR-205-5p. Considering the ZEB1 functions, this overexpression indicates enhancement of metastatic potential of lymphogenously disseminated BC cells. In CD45-DB samples, downregulated miR-205-5p was found in those expressing epithelial and/or mesenchymal markers (CTC+) that could contribute to insusceptibility and survival of hematogenously disseminated BC cells mediated by increased expression of several targets including ZEB1. Conclusions: miR-205-5p and potentially ZEB1 gene are promising candidates for markers of metastatic potential in ductal BC.
Keywords: invasive ductal breast cancer; CDH1 gene; EMT genes; miRNA and mRNA expression; E-cadherin invasive ductal breast cancer; CDH1 gene; EMT genes; miRNA and mRNA expression; E-cadherin

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MDPI and ACS Style

Kalinkova, L.; Nikolaieva, N.; Smolkova, B.; Ciernikova, S.; Kajo, K.; Bella, V.; Kajabova, V.H.; Kosnacova, H.; Minarik, G.; Fridrichova, I. miR-205-5p Downregulation and ZEB1 Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer. Int. J. Mol. Sci. 2022, 23, 103. https://doi.org/10.3390/ijms23010103

AMA Style

Kalinkova L, Nikolaieva N, Smolkova B, Ciernikova S, Kajo K, Bella V, Kajabova VH, Kosnacova H, Minarik G, Fridrichova I. miR-205-5p Downregulation and ZEB1 Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer. International Journal of Molecular Sciences. 2022; 23(1):103. https://doi.org/10.3390/ijms23010103

Chicago/Turabian Style

Kalinkova, Lenka, Nataliia Nikolaieva, Bozena Smolkova, Sona Ciernikova, Karol Kajo, Vladimir Bella, Viera Horvathova Kajabova, Helena Kosnacova, Gabriel Minarik, and Ivana Fridrichova. 2022. "miR-205-5p Downregulation and ZEB1 Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer" International Journal of Molecular Sciences 23, no. 1: 103. https://doi.org/10.3390/ijms23010103

APA Style

Kalinkova, L., Nikolaieva, N., Smolkova, B., Ciernikova, S., Kajo, K., Bella, V., Kajabova, V. H., Kosnacova, H., Minarik, G., & Fridrichova, I. (2022). miR-205-5p Downregulation and ZEB1 Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer. International Journal of Molecular Sciences, 23(1), 103. https://doi.org/10.3390/ijms23010103

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