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

Arpita Ghosh; Nihar Ranjan; Liuwei Jiang; Asgar Hussain Ansari; Natalya Degyatoreva; Shivaksh Ahluwalia; Dev P Arya; Souvik Maiti

doi:10.1016/j.omtn.2021.12.027

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

Mol Ther Nucleic Acids. 2021 Dec 21:27:685-698. doi: 10.1016/j.omtn.2021.12.027. eCollection 2022 Mar 8.

Authors

Arpita Ghosh^{1

2}, Nihar Ranjan³, Liuwei Jiang³, Asgar Hussain Ansari^{1

2}, Natalya Degyatoreva⁴, Shivaksh Ahluwalia^{1

5}, Dev P Arya^{3

4}, Souvik Maiti^{1

2}

Affiliations

¹ CSIR-Institute of Genomics & Integrative Biology, Mathura Road, Delhi 110025, India.
² Academy of Scientific & Innovative Research, CSIR- Human Resource Development Centre (CSIR-HRDC) Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad 201 002, Uttar Pradesh, India.
³ Department of Chemistry, Clemson University, Clemson, SC 29634, USA.
⁴ NUBAD LLC, Greenville, SC 29605, USA.
⁵ Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, Delhi 110016, India.

Abstract

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 become more 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.

Keywords: EMT; breast cancer; epithelial to mesenchymal transition; miR-21; neomycin derivatives; non-coding RNAs; onco-miR.