CKIP-1 silencing suppresses OSCC via mitochondrial homeostasis-associated TFAM/cGAS-STING signalling axis

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Oral squamous cell carcinoma (OSCC) lacks effective treatment targets.
• Casein kinase 2 interacting protein 1 (CKIP-1) is a scaffold protein implicated in various diseases, but its role in OSCC is unknown.

Purpose of the Study:

• To investigate the regulatory role of CKIP-1 in OSCC.
• To elucidate the underlying molecular mechanisms of CKIP-1's action in OSCC.

Main Methods:

• Analysis of CKIP-1 expression in OSCC tissues and cell lines.
• Gain- and loss-of-function experiments to assess CKIP-1's impact on OSCC cell behavior.
• Investigation of mitochondrial homeostasis markers, including mitochondrial transcription factor A (TFAM), reactive oxygen species (ROS), mitochondrial membrane potential, and the cGAS-STING pathway.
• Utilized tetramethylpyrazine (TMP) to inhibit TFAM degradation and confirm pathway involvement.

Main Results:

• CKIP-1 expression is elevated in OSCC tissues and cell lines.
• CKIP-1 silencing suppressed OSCC cell malignant behaviors, enhanced apoptosis, and inhibited tumor growth.
• Silencing CKIP-1 led to TFAM downregulation, increased ROS production, decreased mitochondrial membrane potential, and activated the cGAS-STING pathway.
• The TFAM/cGAS-STING axis was confirmed to be involved in CKIP-1-silenced OSCC cells.

Conclusions:

• CKIP-1 plays a significant role in promoting OSCC progression.
• CKIP-1 silencing antagonizes OSCC via the TFAM/cGAS-STING axis, impacting mitochondrial homeostasis.
• CKIP-1 represents a potential therapeutic target for oral squamous cell carcinoma treatment.