Integrative Investigation of Flavonoids Targeting YBX1 Protein-Protein Interaction Network in Breast Cancer: From Computational Analysis to Experimental Validation

Overview

Journal Mol Biotechnol

Publisher Springer

Specialties Biotechnology
Molecular Biology

Date 2024 Nov 20

PMID 39565541

Authors

Presanna Kumar Sreelekshmi

Suresh Kumar Pooja

Niranjan Vidya

Skariyachan Sinosh

Venkatesh Thejaswini

Affiliations

Soon will be listed here.

Abstract

Y-box-binding protein 1 (YBX1) is a multifunctional oncoprotein with its nuclear localization contributing to chemo-resistance in breast cancer. Through its interactions with various proteins and lncRNAs, YBX1 promotes cancer cell migration, invasion, and metastasis. Despite its significant role in cancer progression, studies on YBX1's protein-protein interactions (PPIs) remain limited. Flavonoids are natural compounds with anticancer properties that inhibit metastasis, modulate immunity, and induce apoptosis, with minimal systemic toxicity, making them strong candidates for cancer therapy. Targeting PPIs offers a promising approach for cancer therapy and flavonoids, with their anticancer properties, may modulate these interactions. Our study focused on the YBX1 PPI network, specifically targeting HSPA1A, IGF2BP1, MECP2, G3BP1, EWSR1, PURA, and SYNCRIP. We selected four flavonoids Quercetin, Fisetin, Rutin, and Myricitrin based on literature and conducted 26 docking sessions. Further ADMET analysis indicated Quercetin and Fisetin as more favorable for drug-likeness parameters than Rutin and Myricitrin, which was underscored by MD simulation data. In vitro studies showed that Quercetin and Fisetin downregulated YBX1 expression in a dose-dependent manner (50 μM to 150 μM) in MCF-7 cells. Our study provides a preliminary understanding of YBX1 PPI and the potential of flavonoids to disrupt these interactions. This study investigates the potential of flavonoids to target YBX1 PPIs, providing insights into novel therapeutic strategies for YBX1-driven cancers.

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