Affiliation:
1. Liaoning University of Traditional Chinese Medicine Shenyang China
2. Department of Oncology The Center Hospital of Enshi Tujia and Miao Autonomous Prefecture Enshi China
3. Department of Otolaryngology – Head and Neck Surgery The Center Hospital of Enshi Tujia and Miao Autonomous Prefecture Enshi China
4. The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine Shenyang China
Abstract
AbstractBackgroundCircular RNAs (circRNAs) are an intriguing family of RNA molecules due to their crucial roles in the pathogenesis of oral squamous cell carcinoma (OSCC). Here, we sought to define the action of human circ_0004674 in OSCC progression.MethodsThe functional role of circ_0004674 was validated by determining its effect on cell growth, apoptosis, and tube formation ability of OSCC cells. For protein quantification, a western blot or immunohistochemistry method was applied. The interaction between miR‐139‐5p and circ_0004674 or zinc finger and BTB domain containing 2 (ZBTB2) was predicted by online algorithms, and their relationships were confirmed by dual‐luciferase reporter and RIP assays. Xenograft models were established to uncover circ_0004674's role in tumor growth.ResultsCirc_0004674 expression was upregulated in OSCC. Functionally, knocking down circ_0004674 led to suppressed OSCC cell progression in vitro and delayed tumor growth in vivo. Mechanistically, circ_0004674 post‐transcriptionally controlled ZBTB2 expression by competitively pairing to miR‐139‐5p. Furthermore, the deficiency of miR‐139‐5p abated circ_0004674 silencing‐mediated OSCC cell progression repression, and augmentation of ZBTB2 reversed the anticancer effect of miR‐139‐5p on OSCC.ConclusionOur findings uncover a novel regulatory cascade, the circ_0004674/miR‐139‐5p/ZBTB2 axis, with the ability to affect OSCC development in vitro and in vivo, providing a potential opportunity for development of OSCC therapy.