The Regulatory Mechanism and Value in Early Diagnosis and Prognosis Assessment of miR-4448 in Breast Cancer

Breast cancer (BC) is heterogeneous malignancy and the most common cancer among women globally. It emphasized the continuous need for effective strategies for early diagnosis and treatment. This study aimed to elucidate the regulatory mechanism of miR-4448 in BC and evaluate its value in early diagnosis and prognosis.

This analysis included 68 patients with BC. The expression levels of miR-4448 and thiamin pyrophosphokinase 1 (TPK1) were measured using RT-qPCR experiments. The diagnostic value of miR-4448 for BC was assessed via ROC analysis. The association between miR-4448 and patient survival was estimated using Multivariate Cox regression analysis and Kaplan-Meier (K-M) analysis. The effects of miR-4448 and TPK1 on the migration, invasion and proliferation of MDA-MB-231 and MCF-7 cells were determined by CCK8 and Transwell experiments. Dual luciferase reporter assay was performed to validate TPK1 as a direct target of miR-4448, and the correlation between their expression was confirmed by Pearson analysis.

Compared with the healthy controls, the level of TPK1 in the serum of BC patients was elevated, while miR-4448 levels was significantly reduced. MiR-4448 demonstrated substantial diagnostic value for BC. Low miR-4448 expression was associated with poorer survival outcomes. Inhibition of miR-4448 promoted the migration, invasion and proliferation abilities of BC cells. TPK1 was confirmed as a direct target of miR-4448, with their expression showing a significant negative correlation. Importantly, silencing TPK1 effectively reversed the protumorigenic effects induced by miR-4448 inhibition.

The study identifies miR-4448 as a potential biomarker for the early diagnosis and prognosis of BC. Inhibiting miR-4448 can promote the development of BC by negatively regulating TPK1.