Metastasis Inhibition by Cell Type Specific Expression of BRMS1 Gene under The Regulation of miR200 Family Response Elements
Objective: Specific expression of therapeutic genes in cancer therapy has been per used for many years. One of the innovative strategies that have recently been introduced is employing miRNA response elements (MREs) of microRNAs (whose expression are reduced or inhibited in cancerous cells) into t...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Royan Institute (ACECR), Tehran
2021-07-01
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| Series: | Cell Journal |
| Subjects: | |
| Online Access: | https://celljournal.org/journal/article/fulltext/metastasis-inhibition-by-cell-type-specific-expression-of-brms1-gene-under-the-regulation-of-mir200-family-mres.pdf |
| Summary: | Objective: Specific expression of therapeutic genes in cancer therapy has been per used for many years. One of the
innovative strategies that have recently been introduced is employing miRNA response elements (MREs) of microRNAs
(whose expression are reduced or inhibited in cancerous cells) into the 3´UTR of the therapeutic genes for their specific
expression. Accordingly, MREs of anti-metastatic miRNA family have been used in 3´UTR of the metastasis suppressor
gene in the corresponding cells to evaluate the level of metastatic behavior.
Material and Methods: In this experimental study, 3´UTR of the ZEB1 gene with 592 bp length, encompassing multiple
MREs of miR-141, miR-429, miR-200b and miR-200c, was employed to replace BRMS1 3´UTR. The obtained vector
was then assessed in the context of MCF-10A, MDA-MB231 and MCF-7 cells.
Results: It was shown that the employed MREs are able to up-regulate BRMS expression in the metastatic MDAMB231
cells (almost 3.5-fold increase), while it was significantly reduced within tumorigenic/non-metastatic MCF-7
cells. Specific expression of BRMS1 in metastatic cells led to a significant reduction in their migratory and invasive
characteristics (about 65% and 55%, respectively). Two-tailed student’s t test was utilized for statistical analysis.
Conclusion: It was demonstrated that a chimeric vector containing BRMS1 which is regulated by miR-200 family
response element may represent a promising therapeutic tool. This is due to the capability of the chimeric vector for
cell type-specific expression of anti-metastatic genes with lowest side-effects. It consequently prohibits the invasive
characteristics of metastatic cells. |
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| ISSN: | 2228-5806 2228-5814 |