ÜÇLÜ NEGATİF MEME KANSERİ HÜCRELERİNDE TWIST1 TARAFINDAN FARKLI ŞEKİLDE DÜZENLENEN miRNA’LAR

Year 2024, Volume: 25 Issue: 4, 396 - 411, 22.12.2024

Bahadir Ozturk , Akın Kol , Suray Pehlivanoğlu , Fatma Şengül Bağ

https://doi.org/10.69601/meandrosmdj.1557035

Abstract

Amaç: Meme kanseri (BC), kadınlarda en yaygın görülen kanser olup kanserle ilişkili ölümlerin en yaygın ikinci nedenidir. MikroRNA'lar (miRNA'lar), gen ekspresyonunu transkripsiyon sonrası düzeyde düzenleyen kısa, kodlayıcı olmayan RNA molekülleridir ve karsinogenez, kanser hücre proliferasyonu ve metastaz ile ilişkili gen ekspresyonunun bozulmasında merkezi bir rol oynarlar. Twist1, E-box motiflerine bağlanan ve hücresel mekanizmalarda belirleyici olan pozitif veya negatif bir düzenleyici olarak genlerin transkripsiyonel aktivitesini kontrol eden bir transkripsiyon faktörüdür. Bu bağlamda, Twist1 kanser ilerlemesi ile ilişkili miRNA'ların ekspresyonunu da düzenler. Bu çalışmada, üçlü negatif meme kanseri (TNBC) MDA-MB-231 hücrelerinde Twist1 tarafından doğrudan düzenlenen olası miRNA'ların ekspresyon değişikliklerini araştırmayı amaçladık.
Gereç ve Yöntemler: Bu çalışmada, üçlü negatif meme kanseri ile ilişkili olabileceği öngörülen toplam 43 miRNA geni değerlendirilmiştir. Twist1'e hedef olan miRNA genlerini belirlemek amacıyla, MDA-MB-231 TNBC hücrelerinde antisens oligonükleotidler aracılığıyla endojen yüksek düzeydeki Twist1 ekspresyonu baskılanmıştır. Twist1 baskılanmış hücrelerdeki farklı miRNA ekspresyon düzeyleri, kontrol grubu ile karşılaştırılarak kantitatif gerçek zamanlı PCR (qRT-PCR) analizi ile değerlendirilmiştir.
Bulgular: Twist1 baskılanması, miR-1-1 ve miR-210-3p ekspresyonunda artışa, miR-193b-3p, miR-181b-5p ve miR-148a-3p ekspresyonunda ise azalmaya neden olmuştur.
Sonuç: Bu çalışma, invazyon, metastaz ve apoptoz ile ilişkili belirli miRNA’ların ekspresyon düzeylerinin, üçlü negatif meme kanseri hücrelerinde Twist1 tarafından kontrol edildiğini göstermektedir.

Keywords

Meme kanseri, MDA-MB-231, mikroRNA, Twist1

Project Number

17202072

DIFFERENTIALLY REGULATED MIRNAS BY TWIST1 IN TRIPLE NEGATIVE BREAST CANCER CELLS

Abstract

Objective: Breast cancer (BC) is the most common cancer in women and the second leading cause of cancer-related deaths. MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression post-transcriptionally and play a central role in the dysregulation of gene expression associated with carcinogenesis, cancer cell proliferation and metastasis. Twist1 is a transcription factor that binds to E-box motifs and controls the transcriptional activity of genes as a positive or negative regulator decisive in the cellular mechanisms. Accordingly, Twist1 also regulates the expression of miRNAs that are associated with cancer progression. In present study, we aimed to investigate the expressional changes of possible miRNAs directly regulated by Twist1 in triple negative breast cancer MDA-MB-231 cells.
Materials and Methods: In this study, a total of 43 miRNA genes were evaluated that predicted might be associated with triple negative breast cancer. To determine the Twist1-targeted miRNA genes, endogenous high level Twist1 expression was suppressed through the antisense oligonucleotides in MDA-MB-231 TNBC cells. Differential miRNA expression levels were analyzed by real time PCR analysis in Twist1-suppressed cells compare to control.
Results: Twist1 suppression leads to an increase in miR-1-1 and miR-210-3p expression, while a decrease in miR-193b-3p, miR-181b-5p, and miR-148a-3p expression.
Conclusion: This study shows that the expression levels of certain miRNAs linked to invasion, metastasis, and apoptosis are controlled by Twist1 in triple negative breast cancer cells.

Keywords

Breast cancer, MDA-MB-231, microRNA, Twist1

Ethical Statement

This study protocol was reviewed and approved by Selcuk University Faculty of Medicine Ethics Committee, approval number 2024/113.

Supporting Institution

Funding for this study was provided by Selçuk University Scientific Research Projects Coordination Office, grant number 17202072.

Project Number

17202072

Thanks

We would like to thank Selçuk University Scientific Research Projects Coordination Office.

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