miR-205-5p Downregulation and <i>ZEB1</i> Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer
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 epith...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/1/103 |
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| author | Lenka Kalinkova Nataliia Nikolaieva Bozena Smolkova Sona Ciernikova Karol Kajo Vladimir Bella Viera Horvathova Kajabova Helena Kosnacova Gabriel Minarik Ivana Fridrichova |
| author_facet | Lenka Kalinkova Nataliia Nikolaieva Bozena Smolkova Sona Ciernikova Karol Kajo Vladimir Bella Viera Horvathova Kajabova Helena Kosnacova Gabriel Minarik Ivana Fridrichova |
| author_sort | Lenka Kalinkova |
| collection | DOAJ |
| description | 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 <i>CDH1</i>/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 <i>CDH1</i> regulating associations previously described in cell lines. However, we did detect extremely high <i>ZEB1</i> 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 <i>ZEB1</i>. Conclusions: miR-205-5p and potentially <i>ZEB1</i> gene are promising candidates for markers of metastatic potential in ductal BC. |
| first_indexed | 2024-03-10T03:40:44Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:40:44Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-af807961b42f4275a4a61ff47a876eca2023-11-23T11:34:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0123110310.3390/ijms23010103miR-205-5p Downregulation and <i>ZEB1</i> Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast CancerLenka Kalinkova0Nataliia Nikolaieva1Bozena Smolkova2Sona Ciernikova3Karol Kajo4Vladimir Bella5Viera Horvathova Kajabova6Helena Kosnacova7Gabriel Minarik8Ivana Fridrichova9Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, SlovakiaDepartment of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, SlovakiaDepartment of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, SlovakiaDepartment of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, SlovakiaDepartment of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, SlovakiaDepartment of Senology, St. Elisabeth Cancer Institute, 81250 Bratislava, SlovakiaDepartment of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, SlovakiaDepartment of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, SlovakiaInstitute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, SlovakiaDepartment of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 84505 Bratislava, SlovakiaBackground: 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 <i>CDH1</i>/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 <i>CDH1</i> regulating associations previously described in cell lines. However, we did detect extremely high <i>ZEB1</i> 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 <i>ZEB1</i>. Conclusions: miR-205-5p and potentially <i>ZEB1</i> gene are promising candidates for markers of metastatic potential in ductal BC.https://www.mdpi.com/1422-0067/23/1/103invasive ductal breast cancer<i>CDH1</i> geneEMT genesmiRNA and mRNA expressionE-cadherin |
| spellingShingle | Lenka Kalinkova Nataliia Nikolaieva Bozena Smolkova Sona Ciernikova Karol Kajo Vladimir Bella Viera Horvathova Kajabova Helena Kosnacova Gabriel Minarik Ivana Fridrichova miR-205-5p Downregulation and <i>ZEB1</i> Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer International Journal of Molecular Sciences invasive ductal breast cancer <i>CDH1</i> gene EMT genes miRNA and mRNA expression E-cadherin |
| title | miR-205-5p Downregulation and <i>ZEB1</i> Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer |
| title_full | miR-205-5p Downregulation and <i>ZEB1</i> Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer |
| title_fullStr | miR-205-5p Downregulation and <i>ZEB1</i> Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer |
| title_full_unstemmed | miR-205-5p Downregulation and <i>ZEB1</i> Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer |
| title_short | miR-205-5p Downregulation and <i>ZEB1</i> Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer |
| title_sort | mir 205 5p downregulation and i zeb1 i upregulation characterize the disseminated tumor cells in patients with invasive ductal breast cancer |
| topic | invasive ductal breast cancer <i>CDH1</i> gene EMT genes miRNA and mRNA expression E-cadherin |
| url | https://www.mdpi.com/1422-0067/23/1/103 |
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