Adamts5 Modulates Breast Cancer Development As a Diagnostic Biomarker and Potential Tumour Suppressor, Regulated by Baiap2-As1, Crnde and Hsa-Mir-135B-3P: Integrated Systems Biology and Experimental Approach Publisher Pubmed



N Tavousi NAJMEH ; Q Taqizadeh QAZAL ; E Nasiriyan ELNAZ ; P Tabaeian PARASTOO ; M Rezaei MOHAMMAD ; M Azadeh MANSOUREH
Source: IET Systems Biology Published:2025

Abstract

ADAMTS5, a member of the ADAMTS family, exhibits crucial biological roles, including protein shedding, proteolysis, and cell migration. Its relevance in breast cancer (BC) was explored through an integrative approach combining high-throughput analyses, database validations, and experimental confirmation. ADAMTS5 expression was significantly reduced in BC samples, as verified by microarray analysis, qRT-PCR, and public database resources. A protein–protein interaction network revealed five proteins—COL10A1, COL11A1, COMP, MMP1 and SDC1—that interact with ADAMTS5 and are primarily associated with the ECM-receptor interaction pathway. These proteins also engage in cell cycle checkpoint signalling, emphasising their potential role in tumour progression. Survival analysis of BC samples identified a novel prognostic signature based on ADAMTS5-related proteins. The study extended to coding and noncoding RNA interactions, identifying lncRNAs as key regulators. CRNDE acts as a ceRNA for ADAMTS5, modulating its expression via hsa-miR-135b-3p. Meanwhile, BAIAP2-AS1 interacts directly with ADAMTS5, offering another layer of regulatory control and prognostic value. These findings position ADAMTS5 as a vital player in BC biology, with its low expression linked to critical pathways and survival outcomes. The identified lncRNA-mediated regulatory mechanisms add depth to understanding ADAMTS5's role and suggest potential targets for therapeutic development. This study underscores ADAMTS5's potential as a biomarker and its broader implications in unravelling BC molecular mechanisms. © 2025 Elsevier B.V., All rights reserved.