Head and neck squamous cell carcinoma (
HNSCC) is the sixth most common
cancer in the world, the 5-year survival rate of patients with
HNSCC is still about 50% due to frequent
metastasis and recurrence.
Circular RNAs (
circRNAs) have been characterized as key regulators of gene expression in numerous
malignancies. However, the role of
circRNA in
HNSCC metastasis remains largely unknown. Here, we demonstrated that the circRFWD3 was significantly upregulated in
HNSCC tissues and cell lines by
circRNA microarray analysis and qPCR. Notably, high expression of circRFWD3 is related to highly aggressive
HNSCC cell lines and
lymph node metastasis in
HNSCC patients. After that, Sanger sequencing,
RNase R, and
actinomycin D assay were performed to verify the ring structure of circRFWD3. Then functional experiments found it could promote the
metastasis of
HNSCC cells both in vitro and in vivo. Mechanistically, a dual-
luciferase reporter assay, FISH, RIP,
RNA pull-down,
RNA-seq, and western blot experiments were employed and found that circRFWD3 served as a
miRNAs sponge for miR-27a/27b, leading to the upregulation of PPARγ, and then promoted
HNSCC metastasis via NF-κB/MMP13 pathway. Finally, ISH and IHC were carried out to determine the expression levels and clinical significances of circRFWD3 and PPARγ in clinical cohorts of
HNSCC. According to the analysis results from two independent
HNSCC cohorts, upregulated expression of circRFWD3 and PPARγ were positively associated with worse survival in patients with
HNSCC. Overall, our results uncover that circRFWD3 acts a critical role in promoting the aggressiveness of
HNSCC cells and is a prognostic marker for the disease, indicating that circRFWD3 may act as a potential therapeutic target in
HNSCC.