Molecular Mechanisms of circKIF4A in Breast Cancer Progression.

Abstract

Aim: Breast cancer (BC) is the most frequently diagnosed malignancy worldwide, necessitating continued research into its molecular mechanisms. Circular RNAs (circRNAs) are increasingly recognized for their role in various cancers, including BC. This study explores the role of circRNA kinesin family member 4A (circKIF4A) in BC progression and its underlying molecular mechanisms.

Methods: BC cell lines were cultured, and circKIF4A expression was knocked down. Cell viability, proliferation, migration, and invasion were assessed using the Cell Counting Kit-8, colony formation assay, and Transwell assays. The expression of circKIF4A, miR-874-3p, and glycerophosphodiester phosphodiesterase domain-containing 5 (GDPD5) was quantified using qRT-PCR and Western blot analysis. Subcellular fractionation was performed to localize circKIF4A within the cell. The interactions between circKIF4A and miR-874-3p, as well as between miR-874-3p and GDPD5, were evaluated using RNA pull-down and dual-luciferase assays. Rescue experiments were conducted with miR-874-3p inhibition or GDPD5 overexpression to confirm the mechanistic pathway.

Results: circKIF4A was found to be upregulated in BC cells. Its knockdown significantly inhibited cell proliferation, migration, and invasion. circKIF4A acts as a sponge for miR-874-3p, reducing its expression. miR-874-3p targets and suppresses GDPD5, a key regulator in BC cell growth. Silencing miR-874-3p or overexpressing GDPD5 reversed the tumor-suppressive effects of circKIF4A knockdown.

Conclusion: circKIF4A promotes BC cell proliferation and invasiveness by regulating the miR-874-3p/GDPD5 axis. These findings highlight a potential therapeutic target in BC and contribute to the understanding of circRNA involvement in cancer progression.