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

Abstract

AbstractLimited effective targets have challenged the treatment of oral squamous cell carcinoma (OSCC). Casein kinase 2 interacting protein 1 (CKIP‐1) is a scaffold protein involved in various diseases. However, the role of CKIP‐1 in OSCC remains unclear. The aim of this study was to explore the regulatory role of CKIP‐1 in OSCC, as well as the involved mechanism. First, higher expression of CKIP‐1 in OSCC tissues and cell lines were found. Series of gain‐ and loss‐of‐function experiments demonstrated suppressed malignant behaviours and enhanced apoptosis of OSCC cells when CKIP‐1 was silenced. Also, inhibited tumour growth in CKIP‐1‐silenced group were proved. Further, mitochondrial transcription factor A (TFAM) downregulation, increased ROS production, decreased mitochondrial membrane potential and cGAS‐STING activation in CKIP‐1‐silenced group were observed. The involvement of mitochondrial homeostasis‐related TFAM/cGAS‐STING axis in CKIP‐1‐silenced OSCC cells was finally demonstrated by tetramethylpyrazine (TMP) that inhibits TFAM degradation. Taken together, our study demonstrated that CKIP‐1 silencing could significantly antagonize OSCC via TFAM/cGAS‐STING axis, which may provide a candidate target for OSCC treatment.