MicroRNAs and Their Targets Could Have a Crucial Role in Breast Cancer Drug Resistance: A Bioinformatics Research

Year 2024, , 458 - 464, 31.08.2024

Murat Kaya

https://doi.org/10.54005/geneltip.1431670

Abstract

Background: MicroRNAs(miRNAs) have been demonstrated to contribute to cancer development by playing essential roles in processes including proliferation, migration, invasion, and metastasis. One of the most serious issues in breast cancer (BRCA) is drug resistance. Recent research suggests that miRNAs may possibly play a role in drug resistance. Using diverse datasets and in silico approaches, we focused on the BRCA/drug resistance/miRNA/mRNA link in our study.
Methods: GSE73736 and GSE71142 geo datasets (for miRNAs) and GSE162187 geodataset (for genes) were obtained from the GEO database to detect differently expressed miRNAs and genes using the R software “LIMMA” package. Potential target genes of screened differentially expressed miRNAs (DE-miRNAs) were predicted using miRMap, miRTarbase, and miRNet tools. Differently expressed genes (DE-genes) were filtered and common DE-genes were identified via TCGA data and miRNet. Afterward, Enrichr, and Funrich tools were used to perform GO annotation and KEGG pathway enrichment analysis. KMplot and GEPIA2 web tools were utilized to investigate further hub miRNAs and genes' expression and prognostic effects.
Results: 3 miRNAs that were considerably downregulated and had prognostic significance in BRCA were identified using the criteria defined in the investigated geo datasets. MiR-586, which is expected to be more closely linked to BRCA, has been found to have the ability to target 5 genes involved in BRCA resistance to therapy. GO, KEGG, and survival analysis showed that the probable target genes of miR-586 could be closely connected to BRCA.
Conclusion: In this study, a comprehensive BRCA-drug resistance-miRNA-gene network was established and new targets for the treatment and prognosis of BRCA were revealed using bioinformatics data.

Keywords

Breast Cancer, Drug Resistance, microRNA, Bioinformatics

MikroRNA’lar ve Hedefleri Meme Kanseri İlaç Direncinde Önemli Bir Role Sahip Olabilir: Biyoinformatik Bir Araştırma

Abstract

Amaç: MikroRNA’ların (miRNA’ların) hücre çoğalması, göç, istila ve metastaz gibi süreçlerde önemli roller oynayarak kanser gelişimine katkıda bulunduğu gösterilmiştir. Meme kanserinde (MK) en ciddi sorunlardan biri ilaç direncidir. Son araştırmalar, miRNA’ların ilaç direncinde rol oynayabileceğini öne sürmektedir. Çalışmamızda çeşitli veri setleri ve in silico yaklaşımlar kullanılarak MK/ilaç direnci/miRNA bağlantısı araştırılmıştır.
Gereç ve Yöntem: Geo veritabanından GSE73736 ve GSE71142 veri setleri (miRNA’lar için) ve GSE162187 veri seti (genler için) indirilerek R yazılımı “LIMMA” paketi aracılığıyla farklı şekilde ifade edilen miRNA’lar ve genler tespit edilmiştir. Farklı şekilde eksprese edilen miRNA’ların (DE-miRNA’lar) potansiyel hedef genleri, miRMap, miRTarbase ve miRNet araçları kullanılarak tahmin edildi. İfade düzeyi farklı olan genler (DE-genler) filtrelenmiş olup TCGA verileri ve miRNet’te ortak olan genler belirlenmiştir. Daha sonra GO ve KEGG ilişkilendirme analizleri Enrichr ve Funrich araçlarıyla yapılmıştır. Hub miRNA ve genlerin ekspresyon düzeyleri ve prognostik etkileri KMplot ve GEPIA2 web araçları kullanılarak araştırılmıştır.
Bulgular: MK’da önemli ölçüde ifadesi azalmış ve prognostik önemi olan 3 miRNA tespit edilmiştir. MK ile daha yakından bağlantılı olabileceği düşünülen miR-586’nın, MK’nın tedaviye direncinde rol oynayan 5 geni hedefleme poansiyeline sahip olduğu görülmüştür. GO ve KEGG analizlerinde, miR-586’nın olası hedef genlerinin MK ile yakından ilişkili olabileceği gösterilmiştir.
Sonuç: Bu çalışmada kapsamlı bir MK ilaç direnci-miRNA-gen ağları araştırılmıştır. Çalışmada biyoinformatik veriler kullanılarak MK’nın tedavi ve prognozuna yönelik yeni veriler ortaya çıkarılmıştır.

Keywords

Meme kanseri, İlaç direnci, mikroRNA, Biyoinformatik

Ethical Statement

Bu çalışmanın, özgün bir çalışma olduğunu; çalışmanın hazırlık, veri toplama, analiz ve bilgilerin sunumu olmak üzere tüm aşamalarından bilimsel etik ilke ve kurallarına uygun davrandığımı; bu çalışma kapsamında elde edilmeyen tüm veri ve bilgiler için kaynak gösterdiğimi ve bu kaynaklara kaynakçada yer verdiğimi; kullanılan verilerde herhangi bir değişiklik yapmadığımı, çalışmanın Committee on Publication Ethics (COPE)' in tüm şartlarını ve koşullarını kabul ederek etik görev ve sorumluluklara riayet ettiğimi beyan ederim. Herhangi bir zamanda, çalışmayla ilgili yaptığım bu beyana aykırı bir durumun saptanması durumunda, ortaya çıkacak tüm ahlaki ve hukuki sonuçlara razı olduğumu bildiririm.

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