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.
MiRNA targets within gene transcripts were predicted in silico using the TargetScan software.
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.
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.
Has not received any funding.
The author has declared no conflicts of interest.