NDRG1 regulates osteosarcoma cells via mediating the mitochondrial function and CSCs differentiation

Area of Science:

• Oncology
• Cell Biology
• Mitochondrial Biology

Background:

• Osteosarcoma (OS) malignancy, metastasis, and therapy resistance are linked to cancer stem cells (CSCs).
• Mitochondria-targeted apoptosis is a key strategy in tumor therapy.
• The role of N-myc downstream-regulated gene 1 (NDRG1) in OS CSCs and mitochondrial health remains unclear.

Purpose of the Study:

• To investigate the effect of NDRG1 on cancer stem cells (CSCs) and mitochondrial function in osteosarcoma (OS).

Main Methods:

• Silencing of NDRG1 using siRNA in OS cell lines (MG63, U2OS).
• Assays included Transwell, western blot, RT-qPCR, and mitochondria isolation.
• Determination of CSC differentiation markers and mitochondrial function parameters.

Main Results:

• NDRG1 silencing decreased cell viability and invasion, increasing apoptosis in OS cells.
• Downregulation of NDRG1 affected expression of key proteins involved in invasion (e.g., VEGF, MMPs) and cell adhesion (E-cadherin).
• NDRG1 silencing impaired mitochondrial function, decreasing mitochondrial membrane potential and cytochrome C release, while affecting key mitochondrial proteins (e.g., UCP2, VDAC, PGC-1α, COX2). NDRG1 also regulates CSC differentiation via the Wnt pathway.

Conclusions:

• Silencing NDRG1 damages mitochondrial function and promotes CSC differentiation.
• This process alleviates osteosarcoma progression, highlighting NDRG1 as a potential therapeutic target.