ADAMTS5 modulates breast cancer development as a diagnostic biomarker and potential tumor suppressor, regulating by BAIAP2-AS1, VTI1B, CRNDE, and hsa-miR-135b-3p: integrated systems biology and experimental approach

Abstract

Background: A disintegrin and metalloproteinases (ADAMs) are a novel gene family of proteins that share the metalloproteinase domain with matrix metalloproteinases and have sequence similarities to the reprolysin family of snake venomases (MMPs). They are divided into two classes based on their structural similarities: membrane-anchored ADAM and ADAM with thrombospondin motifs (ADAMTS). These molecules have a role in a number of biological processes, including membrane protein shedding, proteolysis, cell adhesion, cell fusion, and cell migration. Method: In this study, the RNA interaction analysis (miRWalk, lncRRisearch, ENCORI, and lncBase3) and protein interaction analysis (STRING) was performed. Survival, expression, and correlation analyses was performed by ENCORI and GEPIA2. Expression analysis also performed by microarray analysis. GSEA analysis was performed to find top up and down-regulated genes and relevant signaling pathway. Gene ontology analysis was performed by g: Profiler and clusterprofiler. Pathway enrichment was performed by GSEA analysis.ResultsADAMTS5 has a significant low-expression, based on ENCORI (Fold Change: 0.12, FDR < 0.0001), microarray analysis (logFC: -3.791881, adj. P. Val < 0.0001), and qRT-PCR experiment (logFC: -1.975, FC: 0.025, p. value < 0.0001, patients under 40). ADAMTS5 is a potential diagnostic biomarker of BC, based on ROC curve (AUC: 0.75, p. value: 0.0007). mRNA VTI1B, lncRNAs CRNDE and BAIAP2-AS1, and hsa-miR-135a-3b have interaction with ADAMTS5. VTI1B has a significant low-expression (FC: 0.65, FDR: 0.0001). BAIAP2-AS1 is significantly up-regulated (FC: 1.37, FDR: 0.0001). CRNDE is significantly up-regulated (FC: 1.30, FDR: 0.0001). BAIAP2 (log-Rank p: 0.0017, Hazard Ratio: 0.59) and CRNDE (log-Rank p: 0.34, Hazard Ratio: 1.17) are the two potential BC survival predictor.ConclusionIn this study, we performed a differential expression analysis on the expression level of ADAMTS5, VTI1B, and BAIAP2-AS1 in the BC patients for the first time. ADAMTS5 and its correlated oncogene and tumor suppressor RNAs and proteins are the hub therapeutic target of BC. DEGs of the GSE42568 dataset are involve in PPAR and cell cycle checkpoint signaling pathways and during the regulation of mentioned pathway, regulate the BC development. Targeting the expression and interaction of mentioned RNAs can be helpful for the diagnosis, prognosis, and treatment of BC.

MNCR and JPX lncRNAs have a significant oncogenic and biomarker role in the Isfahan Breast cancer population by regulating the MYC expression level: An integrated bioinformatics and experimental approach

“…Previous similar studies mentioned some novel lncRNAs as the potential prognostic and diagnostic biomarkers of cancer [50], [51]. As a suggestion, we offer the same experiments on the two lncRNAs JPX and MINCR, in the different clinicopathological subgroups by the larger samples size.…”

Up-regulation of LINC01010 and lncRNA CASC15 can regulate the p53 signaling pathway and apoptosis process by regulation of PERP expression level as a breast cancer biomarker: Integrated systems biology and experimental approach

“…For example, Tavousi et al in a pre-print mentioned that the regulatory network of ADAMTS5 protein could regulate development of BC (54). Also, Donyavi et al in 2022 revealed that EZH2-related ceRNA axes regulates hepatocellular carcinoma (54). Nevertheless, due to our limitation for obtaining clinical samples, we highly recommend that the same experiment be performed on a bigger samples size for obtaining more validated results about the expression pattern of the three mentioned RNAs.…”

“…Previous studies revealed that performed systems biology approach can be an effective method to nd novel information about the role of different complexes -including the regulatory networks of proteins -in BC development. For example, Tavousi et al in a pre-print mentioned that the regulatory network of ADAMTS5 protein could regulate development of BC (54). Also, Donyavi et al in 2022 revealed that EZH2-related ceRNA axes regulates hepatocellular carcinoma (54).…”

lncRNA HCG11 regulates the expression level of SP1 as a potential prognostic biomarker of BC during the polymerase II transcription process in an HCG11/miR-106a-3p/SP1 axis: integrated bioinformatics and experimental investigation

“…Previous bioinformatics studies demonstrated that the systems biology approach reveals nove information about the molecular mechanism of different cancer types, like HCC (52) and BC (53,54). However, it is highly recommended that the expression level of hsa-miR-106a-3p be evaluated by experimental methods (e.g., qRT-PCR) in the different populations of different cancer types, including BC.…”