Integrative bioinformatics analysis reveals miR-494 and its target genes as predictive biomarkers of trastuzumab-resistant breast cancer

Hermawan, Adam and Putri, Herwandhani (2020) Integrative bioinformatics analysis reveals miR-494 and its target genes as predictive biomarkers of trastuzumab-resistant breast cancer. Journal of the Egyptian National Cancer Institute, 32 (1). ISSN 25890409; 11100362

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Abstract

Background: The focus of trastuzumab resistance biomarkers in recent decades has been on epigenetic and non-coding RNA-based mechanisms. In this study, the potential of miR-494 and its target genes as predictive biomarkers for breast cancer (BC) resistance to trastuzumab was identified. The microarray data were obtained from the GEO database, including GSE101841, GSE75669, and GSE66305. Data processing was conducted using GEO2R to obtain differentially expressed genes (DEGs). Results: The data analysis using GEO2R revealed that DEGs from GSE101841 and GSE75669 consisted of 3 and 135 upregulated miRNAs, respectively. On the other hand, the same analysis revealed 8 and 226 downregulated miRNAs for DEGs from GSE101841 and GSE75669, respectively. A Venn diagram showed that one miR was detectable in serum and tissue samples, namely miR-494. The miR-494 target was predicted using the miRecords database and resulted in 69 target genes. A Venn diagram between miR-494 target genes from miRecords and the mRNA array from GSE66305 revealed three potential targets of CNR1, RBM39, and ZNF207. A Kaplan-Meier survival plot showed that BC patients with a high miR-494 level and a low ZNF207 mRNA level had significantly worse overall survival. Validation of target genes in BC samples and trastuzumab-resistant and -sensitive BC cells with GEPIA and ONCOMINE highlighted the potential of CNR1, RBM39, and ZNF207 as predictive biomarkers of trastuzumab resistance in BC cells. Conclusion: Taken together, these results suggest that miR-494 plays a role in the mechanism of BC resistance to trastuzumab by involving its target genes CNR1, RBM39, and ZNF207. © 2020 Elsevier B.V., All rights reserved.

Item Type: Article
Additional Information: Cited by: 8; All Open Access; Gold Open Access
Uncontrolled Keywords: biological marker; microRNA; microRNA 494; trastuzumab; unclassified drug; cannabinoid 1 receptor; CNR1 protein, human; HCC1 autoantigen; microtubule associated protein; MIRN494 microRNA, human; RNA binding protein; tumor marker; ZNF207 protein, human; Article; bioinformatics; breast cancer; cancer patient; cancer resistance; cnr1 gene; data analysis; down regulation; gene; gene targeting; human; mRNA expression level; overall survival; rbm39 gene; sample; upregulation; znf207 gene; biology; breast tumor; DNA microarray; drug resistance; female; gene expression profiling; gene expression regulation; genetics; information processing; Kaplan Meier method; metabolism; mortality; prognosis; tumor cell line; Biomarkers, Tumor; Breast Neoplasms; Cell Line, Tumor; Computational Biology; Datasets as Topic; Drug Resistance, Neoplasm; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; MicroRNAs; Microtubule-Associated Proteins; Oligonucleotide Array Sequence Analysis; Prognosis; Receptor, Cannabinoid, CB1; RNA-Binding Proteins; Trastuzumab
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Pharmacy
Depositing User: Sri JUNANDI
Date Deposited: 10 Nov 2025 01:57
Last Modified: 10 Nov 2025 01:57
URI: https://ir.lib.ugm.ac.id/id/eprint/23964

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