A Prospective Tumour Marker for Breast Cancer: YWHAB and Its Role in Promoting Oncogenic Phenotypes

Vaishnavi L Gopaul,* Lacey Winstone,* Beatrice G Gatien,* Braydon D Nault, Sujit Maiti, Reid M Opperman, Mousumi Majumder Department of Biology, Brandon University, Brandon, MB, Canada*These authors contributed equally to this workCorrespondence: Mousumi Majumder, Email [email protected]: YWHAB (14-3-3 Beta) was found in the secretome of miR-526b and miR-655 overexpressed breast cancer (BRCA) cell lines. The potential of YWHAB as a therapeutic target or biomarker for BRCA is investigated here.Methods: After YWHAB was knocked down with siRNA, BRCA cell lines were used for in vitro assays (proliferation, migration, epithelial-to-mesenchymal transition). In silico analysis and in situ validation with BRCA plasma and biopsy tissues were used to test YWHAB’s biomarker potential.Results: YWHAB RNA and protein expression are elevated in aggressive BRCA cell lines, and the knockdown of YWHAB inhibited cell migration, proliferation, and EMT in all subtypes of tumour cell lines. YWHAB expression is significantly higher in BRCA biopsy tissue and blood plasma compared to control tissues and benign plasmas. YWHAB is expressed in all hormonal subtypes of BRCA tumours and has shown increased expression in advanced tumour stages. Its high expression is linked to poor patient survival. YWHAB is a sensitivity tumour marker (AUC of 0.7340, p = 0.0012) but is not a promising blood biomarker. Nevertheless, combined with pri-miR-526b, YWHAB mRNA expression shows potential as a BRCA blood biomarker (AUC of 0.711, p = 0.032), which must be validated in a larger sample set.Conclusion: We elucidate the novel role of YWHAB as a therapeutic target in BRCA, given that its inhibition mitigated aggressive phenotypes across all tumour subtypes, including triple-negative breast cancer. Furthermore, YWHAB emerges as a potential tumour marker, exhibiting high expression in metastatic BRCA and correlating with poor patient survival; however, it is not a sensitive blood biomarker. Keywords: breast cancer, microRNA, miRNA, miR-526b, miR-655, YWHAB, 14-3-3 Beta, biomarker, migration, epithelial to mesenchymal transition, proliferation