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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

3289 - First step to metastasis: miRNAome abnormalities impair cell-cell adhesion and facilitate detachment of breast cancer cells

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Topics

Cancer Biology

Tumour Site

Breast Cancer

Presenters

Volodymyr Halytskiy

Citation

Annals of Oncology (2018) 29 (suppl_8): viii1-viii13. 10.1093/annonc/mdy268

Authors

V. Halytskiy

Author affiliations

  • Molecular Immunology Department, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, UA-01030 - Kiev/UA

Resources

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Abstract 3289

Background

In order to metastasize, cancer cells must detach from neighboring cells and extracellular matrix. With regard to data that microRNAs (miRNAs) miR-18, miR-19, miR-21, miR-23, miR-29, miR-155, miR-181, miR-206, miR-210, miR-221/222 and miR-375 are usually overexpressed in breast cancer cells, this research aims to identify in what way the abnormality in miRNA signature can contribute to the disintegration of cell-cell contacts.

Methods

MiRNA targets within gene transcripts were predicted in silico using the TargetScan software.

Results

Targets of overexpressed miRNAs miR-18, miR-23, miR-25, miR-150, miR-181, miR-221/222 and miR-372/373 were found in transcript of CDH1 gene encoding E-cadherin. Transcripts of genes F11R and JAM3 encoding junctional adhesion molecules JAM-A and JAM-C carry targets of miRNAs miR-23, miR-29, miR-155, miR-181 and miR-221/222. Binding sites for miRNAs miR-23 and miR-150 were revealed in transcripts of TJP1 and TJP2 genes encoding tight junction proteins ZO-1 and ZO-2. MiRNAs miR-21, miR-29, miR-155 and miR-375 can silence CLDN1 gene encoding claudin 1. Up-regulated miRNAs miR-19, miR-21 and miR-155 can target transcript of CGN gene encoding cingulin. MiRNAs miR-18, miR-29, miR-155, miR-181 and miR-375 suppress OCLN gene coding occludin. Overexpressed miRNAs miR-21, miR-23, miR-29, miR-155, and miR-221/222 can target transcripts of PVRL1 and PVRL3 genes encoding nectin 1 and 3. In addition, up-regulated miRNAs can silence other genes responsible for cell-cell adhesion - CADM1/3 (encoding nectin-like molecules 2/1), CTNNA1 (alpha-catenin), CTNND1 (p120-catenin) as well as genes encoding tropomyosin 1, vinculin, alpha-actinins.

Conclusions

MiRNAs, hyperexpressed in breast cancer cells, can silence genes encoding E-cadherin and numerous other epithelial junction components. This causes disruption of cell-cell adhesion, and, in addition, affects cell polarity and contact inhibition, predetermines epithelial-mesenchymal transition, detachment, movement and invasiveness of the breast cancer cells.

Clinical trial identification

Legal entity responsible for the study

Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

The author has declared no conflicts of interest.

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