Kaya Murat, Abuaisha Asmaa, Suer Ilknur, Emiroglu Selman, Önder Semen, Onay Ucar Evren, Yenerel Mustafa Nuri, Palanduz Sukru, Cefle Kivanc, Ozturk Sukru, Kurt Zeyneb
Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Medical Genetics, Istanbul University, Capa, Fatih, Istanbul, Turkey.
Research Center, Biruni University, Istanbul, Turkey.
PLoS One. 2025 Jan 9;20(1):e0307420. doi: 10.1371/journal.pone.0307420. eCollection 2025.
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the expression level of the target genes in the cell. Breast cancer is responsible for the majority of cancer-related deaths among women globally. It has been proven that deregulated miRNAs may play an essential role in the progression of breast cancer. It has been shown in many cancers, including breast cancer, that aberrant expression of miRNAs may be associated with drug resistance. This study investigated the effect of let-7b-5p, detected by bioinformatics methods, on Dox resistance through the Aurora Kinase B (AURKB) gene. In silico analysis using publicly available miRNA expression, GEO datasets revealed that let-7b-5p significantly downregulated in BC. Further in silico studies revealed that of the genes among the potential targets of let-7b-5p, AURKB was the most negatively correlated and may be closely associated with Dox resistance. Expression analysis via quantitative PCR confirmed that let-7b-5p was downregulated and AURKB was upregulated in breast cancer tissue samples. Later, functional studies conducted with MCF-10A, MCF-7, and MDA-MB-231 cell lines demonstrated that let-7b-5p inhibits cancer cells through AURKB and sensitizes them to Dox resistance. In conclusion, it has been shown that the let-7b-5p/AURKB axis may be significant in breast cancer progression and the disruption in this axis may contribute to the trigger of Dox resistance.
微小RNA(miRNA)是一类小的非编码RNA,可调节细胞中靶基因的表达水平。乳腺癌是全球女性癌症相关死亡的主要原因。已证实,失调的miRNA可能在乳腺癌进展中起重要作用。在包括乳腺癌在内的许多癌症中已表明,miRNA的异常表达可能与耐药性有关。本研究通过生物信息学方法检测了let-7b-5p对通过极光激酶B(AURKB)基因产生的阿霉素耐药性的影响。使用公开可用的miRNA表达进行的计算机分析,GEO数据集显示let-7b-5p在乳腺癌中显著下调。进一步的计算机研究表明,在let-7b-5p的潜在靶标基因中,AURKB与耐药性的负相关性最强,并且可能与阿霉素耐药性密切相关。通过定量PCR进行的表达分析证实,乳腺癌组织样本中let-7b-5p下调而AURKB上调。随后,对MCF-10A、MCF-7和MDA-MB-231细胞系进行的功能研究表明,let-7b-5p通过AURKB抑制癌细胞并使其对阿霉素耐药性敏感。总之,已表明let-7b-5p/AURKB轴可能在乳腺癌进展中起重要作用,并且该轴的破坏可能导致阿霉素耐药性的触发。