USP34 modulates mitochondrial function in triple-negative breast cancer cells through the eIf3m/MTCH2 axis

Area of Science:

• Molecular Biology
• Oncology
• Biochemistry

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with high recurrence rates.
• Mitochondrial dysfunction is implicated in suppressing TNBC cell proliferation.
• USP34 is overexpressed in TNBC and its role in mitochondrial function requires elucidation.

Purpose of the Study:

• To investigate the role of USP34 in modulating mitochondrial function in TNBC.
• To elucidate the molecular mechanisms by which USP34 influences TNBC progression.

Main Methods:

• Cell proliferation assays (EdU).
• Mitochondrial function assessment (JC-1, MitoSOX Red, Mito-Tracker Red).
• Protein and RNA interaction studies (co-IP, GST-pull down, RIP, RNA-pull down).

Main Results:

• USP34 silencing inhibited TNBC cell proliferation via induced mitochondrial dysfunction.
• USP34 deubiquitinated and stabilized eIF3m protein.
• eIF3m overexpression rescued mitochondrial dysfunction caused by USP34 silencing.
• eIF3m directly bound to the 5'UTR of MTCH2 mRNA, upregulating MTCH2 expression.
• MTCH2 overexpression reversed the negative effects of eIF3m silencing on mitochondrial function.

Conclusions:

• USP34 promotes TNBC progression by stabilizing eIF3m, which enhances MTCH2 expression.
• This USP34/eIF3m/MTCH2 axis maintains mitochondrial function, contributing to TNBC malignancy.
• Targeting USP34 may offer a therapeutic strategy for TNBC.