3rd International Congress of Medical and Health Sciences Research, Ankara, Turkey, 13 - 14 December 2024, pp.291-303, (Full Text)
Breast cancer (BC) is the most diagnosed cancer and the leading cause of cancer mortality in women worldwide. MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs (19 - 24 nucleotides) responsible for the post-transcriptional regulation of gene expression. Since miRNAs play a role in biological processes such as cell differentiation, proliferation, and cell death, elucidating the molecular mechanisms of miRNAs and target genes is crucial for the development of cancer treatment. miR-145-5p is a tumor suppressor miRNA that exhibits decreased expression in several cancers, including BC. In this study, we aimed to investigate the association of miR-145-5p and its potential target genes in BC cells. First, miRDB database was used to identify miR-145-5p target genes. Subsequently, the identified genes were searched in PubMed using keywords such as "gene name," and "breast cancer," to select the most related genes. Afterward, normal human breast epithelial MCF-10A cells and BC MCF-7 cells were cultured. MCF-7 cells were then transfected with 30 pmol miR-145-5p mimic and negative control miRNA mimic by using Lipofectamine reagent. MiR-145-5p and gene expression levels were detected by using quantitative real-time PCR (qPCR). The 2-ΔΔCt method was used to analyze the relative changes in expression. A p-value less than 0.05 was deemed a statistically significant result. As a result of the silico analysis and literature search 4 genes (CDK6, IRS1, UHRF1, and SIX4) were selected as potential targets of miR-145-5p. In expression studies, CDK6, IRS1, and UHRF1 genes were upregulated in the MCF-7 cells compared to MCF-10A cells. Additionally, miR-145-5p mimic-transfected MCF-7 BC cells showed significantly reduced expression of CDK6, IRS1, and UHRF1 genes compared to negative control miRNA mimic transfected cells. Our in vitro and in silico analysis showed that miR-145-5p suppresses BC cells through CDK6, IRS1, and UHRF1 genes. In conclusion, our study highlights the potential role of miR-145-5p and its potential target genes (CDK6, IRS1, and UHRF1) in BC tumorigenesis.