Fine-tuning miR-21 expression and inhibition of EMT in breast cancer cells using aromatic-neomycin derivatives

MicroRNAs (miRs) are a class of endogenously expressed non-coding RNAs that negatively regulate gene expression within cells and participate in maintaining cellular homeostasis. By targeting 3' UTRs of target genes, individual miRs can control a wide array of gene expressions. Previous research has shed light upon the fact that aberrantly expressed miRs within cells can pertain to diseased conditions, such as cancer. Malignancies caused due to miRs are because of the high expression of onco-miRs or feeble expression of tumor-suppressing miRs. Studies have also shown miRs to engage in epithelial to mesenchymal transition (EMT), which allows cancer cells to becomemore invasive and metastasize. miR-21 is an onco-miR highly expressed in breast cancer cells and targets protein PTEN, which abrogates EMT. Therefore, we discuss an approach where in-house-developed peptidic amino sugar molecules have been used to target pre-miR-21 to inhibit miR-21 biogenesis, and hence antagonize its tumor-causing effect and inhibit EMT. Our study shows that small-molecule-based fine-tuning of miR expression can cause genotypic as well as phenotypic changes and also reinstates the potential and importance of nucleic acid therapeutics.

Automated summary

MicroRNAs (miRs) are endogenously expressed non-coding RNAs that regulate gene expression within cells and are involved in maintaining cellular homeostasis. Aberrantly expressed miRs can be associated with diseases such as cancer. miR-21, highly expressed in breast cancer cells, acts as an onco-miR by targeting PTEN protein and promoting epithelial to mesenchymal transition (EMT). This study uses peptidic amino sugar molecules to target pre-miR-21 and inhibit its biogenesis, thereby counteracting its tumor-causing effect and inhibiting EMT.