Silencing of circUSPL1 represses breast cancer progression by targeting miR-1296-5p/MTA1 axis

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Circular RNAs (circRNAs) play a role in various human cancers, including breast cancer (BC).
• circUSPL1 has emerged as a potential regulator of BC progression.
• The precise biological functions and molecular mechanisms of circUSPL1 in BC require further elucidation.

Purpose of the Study:

• To investigate the role and molecular mechanism of circUSPL1 in breast cancer progression.
• To explore the regulatory relationship between circUSPL1, miR-1296-5p, and MTA1 in BC.
• To assess the therapeutic potential of targeting circUSPL1 in BC.

Main Methods:

• Quantitative reverse transcription PCR (qRT-PCR) to measure circUSPL1, miR-1296-5p, and MTA1 expression.
• In vitro assays (colony formation, EdU, wound healing, Transwell, flow cytometry, glycolysis assays) to evaluate BC cell proliferation, migration, invasion, apoptosis, and glycolysis.
• Western blot analysis to assess protein levels of key molecules (Bcl-2, Bax, HK2, GLUT1, MTA1).
• Dual-luciferase reporter and RIP assays to confirm molecular interactions.
• In vivo studies using a murine xenograft model to assess tumor growth.

Main Results:

• circUSPL1 and MTA1 expression were elevated, while miR-1296-5p was reduced in BC tissues and cells.
• circUSPL1 knockdown significantly inhibited BC cell proliferation, migration, invasion, and glycolysis, while promoting apoptosis.
• circUSPL1 directly targets miR-1296-5p, and MTA1 acts downstream of this interaction.
• Overexpression of miR-1296-5p suppressed malignant phenotypes, an effect reversed by MTA1 upregulation.
• Silencing circUSPL1 inhibited tumor growth in vivo by sponging miR-1296-5p and regulating MTA1.

Conclusions:

• circUSPL1 deficiency suppresses BC cell malignant phenotypes by reducing MTA1 expression via the miR-1296-5p pathway.
• circUSPL1 acts as a tumor promoter in breast cancer by sponging miR-1296-5p and regulating MTA1.
• Targeting circUSPL1 may offer a novel therapeutic strategy for breast cancer treatment.