MIR-26-5P INHIBITS THE PROLIFERATION AND MIGRATION OF BREAST CANCER CELLS BY TARGETING THE TUMOR PROTEIN D52

Haili Tang^{1, #}, Ping Yang^{1, #}, XiaoJun Yang¹, Bo Qiu¹, JiWei Gao¹, XiE Hu¹, JingYi Xue², YanMing Dong¹, Dong Fan¹, HuaDong Zhao^{1, *} 

¹Tangdu Hospital, the Second Affiliated Hospital of Air Force Military Medical University - ²Second Clinical Medical College of Shaanxi University of Chinese Medicine

Objective: Breast cancer (BC) is one of the most common malignancies in women worldwide and has a high mortality rate due to tumor metastasis. miRNA plays a crucial role in the occurrence and development of human cancers. This study aims to investigate the biological role of miR-26-5p in BC.

Methods: The expression levels of miR-26-5p in clinical BC samples from data set GSE118782 were analyzed from the GEO database GEO2R. The expression levels of miR-26-5p and TPD52 in BC cells were detected by qRT-PCR analysis. The effect of miR-26-5p on BC cell proliferation was determined by CCK-8 and EdU experiments. Cell scratch and transwell assays were performed to evaluate miR-26-5p-mediated migration and invasion of BC cells. miRNA target analysis tools were used to predict the interacting protein and interacting sequence of miR-26-5p in BC cells. The targeting relationship of miR-26-5p to TPD52 was tested by the luciferase reporter gene assay. The expression level of TPD52 was detected by qRT-PCR and western blot assay to verify the targeted inhibitory effect of miR-26-5p on TPD52.

Results: It was found that the expression level of miR-26-5p was significantly downregulated in BC tissues and cells. Over-expression of miR-26-5p markedly inhibited the proliferation, migration, and invasion abilities of BC cells, while inhibition of miR-26-5p substantially enhanced the proliferation, migration, and invasion abilities of BC cells. Dual-luciferase reporter gene and western blot assays showed that miR-26-5p could directly target inhibition of the expression of TPD52 in BC cells. Over-expression of TPD52 reversed the inhibition of miR-26-5p on BC cell proliferation, migration, and invasion. Similarly, inhibition of TPD52 expression reversed the promotion effect of the miR-26-5p inhibitor on BC cell proliferation, migration, and invasion. 

Conclusion: Our findings suggest that miR-26-5p can enhance BC cell proliferation, migration, and invasion by directly targeting inhibition of the expression of TPD52, suggesting that miR-26-5p and TPD52 may be potential therapeutic targets for BC therapy.