Mitigating the Oncogenic Roles of miR‑629‑5p and miR‑660‑5p Through Direct Binding by Two Potential Drug Targets for Colorectal Cancer Prevention

Abstract 

Background: Many studies have reported the oncogenic roles of microRNA (miRNA)‑629‑5p and miRNA‑660‑5p in various cancers. This study aimed to elucidate the oncogenic roles of miRNA‑629‑5p and miRNA‑660‑5p, focusing on their potential contributions to early colorectal cancer (CRC) detection. Additionally, this research examines the efficacy of Regorafenib and 3,3’‑diindolylmethane (DIM) as therapeutic agents aimed at mitigating the oncogenic activities of these miRNAs by influencing their structural and conformational dynamics, thereby offering a preventive strategy against CRC.

Methods: The study utilized quantitative real‑time polymerase chain reaction (QRT‑PCR) to confirm the overexpression of miR‑629‑5p and miR‑660‑5p in 40 CRC tissues compared to 40 standard samples and their association with clinicopathological factors. Molecular docking and molecular dynamics simulation were used to investigate Regorafenib and DIM binding modes to miR‑629‑5p and miR‑660‑5p.

Results: QRT-PCR showed that miR‑629‑5p and miR‑660‑5p were overexpressed in CRC tissues. In silico molecular docking and dynamic simulation strengthened our hypothesis that Regorafenib and DIM were located in the structures of the mentioned miRNAs, resulting in a slight alteration in their structures during the interaction process.

Conclusions: The study’s findings suggest that miR‑629‑5p and miR‑660‑5p may have potential as predictive biomarkers and treatment targets for Preventing CRC and that Regorafenib and DIM may have miRNA binding properties. They indicated a high affinity to miRNA‑629‑5p compared with miRNA‑660‑5p created a slight change in its structure and can suppress its activity in CRC. However, extra experimental approaches are needed to approve our hypothesis.