miRNA and green tea catechins interactions in breast cancer: a bioinformatics approach

• Published in: The FASEB journal 2022-05, Vol.36 (S1), p.n/a
• Main Authors: Piedra, Giselle, Gonzalez, Christina, Martínez Cardoze, Scarlet, Rodriguez, Yoel, Delgado‐Cruzata, Lissette
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2022.36.S1.R6013

Increased green tea consumption in Asian populations has been linked to decreased breast cancer risk. These green tea chemopreventive properties are attributed to catechins like catechin hydrate (CH), catechin gallate (ECG), and epigallocatechin‐3‐gallate (EGCG). These compounds induce apoptosis and inhibit cell proliferation but the molecular mechanisms underlying these anticancer effects are still unknown. Data suggests it can involve the regulation of microRNAs (miRNAs), small non‐coding RNAs involved in gene expression regulation. A previous study found that regulation of miR‐33a and miR‐122 by epigallocatechin‐3‐gallate resulted from their direct interactions. Less is known about the potential interactions of other miRNAs with catechins. We hypothesize that miRNAs interact directly with catechin compounds, thus interfering with their processing and function. To test this, we conducted a literature search to identify miRNAs previously shown to be relevant in breast carcinogenesis and responsive to catechin exposure. We identified five microRNAs: miR‐25‐3p, miR‐92a‐3p, miR‐93‐5p, miR‐16‐5p, and miR‐19a‐3p, and conducted a structure prediction analysis to determine the likelihood of catechins binding to these miRNAs. Sequences were extracted from miRDBase. RNAfold and RNAstructure web servers were used to refine their secondary structures. iFoldRNA and SimRNAweb programs were used to predict their tertiary structures and the presence of cavities. We found all miRNAs had at least one cavity, indicating they can potentially bind these compounds. We conducted structure‐based molecular docking and used MOE GBV/WSA dG scoring function to rank the screened catechins based on their affinities toward each miRNA. Molecular docking predictions revealed two cavities in miR‐25‐3p that bind to ECG and EGCG, and one cavity that binds to CH. miR‐92a‐3p was found to have two cavities, both of which bind to all ligands. The predictions of miR‐16‐5p, and miR‐19a‐3p revealed one cavity that binds to all three catechins. miR‐93‐5p has a groove that also binds to all ligands. All five miRNAs had scoring function values within the range of ‐4.9181kcal/mol to ‐7.1800kcal/mol. We are using these models to test specific nucleotides interactions with these compounds. Ultimately, our findings will increase knowledge about the molecular mechanisms that mediate catechin action.