MiR-4458 inhibits breast cancer cell growth, migration, and invasiveness by targeting CPSF4

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• CPSF4 is overexpressed in lung and breast cancers (BC), acting as a potential oncogene.
• CPSF4 overexpression correlates with poor prognosis in BC patients.
• Understanding the regulation of CPSF4 is crucial for BC treatment strategies.

Purpose of the Study:

• To investigate microRNAs (miRNAs) targeting CPSF4 to modulate BC cell proliferation.
• To identify specific miRNAs that suppress BC growth by regulating CPSF4.
• To elucidate the molecular mechanisms underlying miR-4458's role in BC.

Main Methods:

• Bioinformatic analysis to predict miRNA targets.
• Luciferase reporter assays to confirm direct targeting of CPSF4 by miR-4458.
• Western blotting to assess protein expression levels (CPSF4, COX-2, h-TERT).
• Cell proliferation, migration, and invasion assays.
• In vivo tumor growth studies in a mouse model.

Main Results:

• miR-4458 was significantly downregulated in BC tissues and cells.
• Overexpression of miR-4458 suppressed BC cell proliferation, migration, and invasion.
• miR-4458 directly targets the 3'-UTR of CPSF4, downregulating CPSF4, COX-2, and h-TERT.
• miR-4458 overexpression inhibited PI3K/AKT and ERK signaling pathways.
• miR-4458 suppressed BC tumor growth in vivo.

Conclusions:

• The miR-4458-CPSF4 axis plays a critical role in BC progression.
• miR-4458 acts as a tumor suppressor by targeting CPSF4 and its downstream genes (COX-2, h-TERT).
• The miR-4458-CPSF4-COX-2-hTERT pathway represents a potential therapeutic target for BC treatment.