circPTPRM can encode a functional polypeptide circPTPRM-187aa to promote papillary thyroid carcinoma progression.

[AIMS] Papillary thyroid carcinoma (PTC) is the most common thyroid tumor, usually with a good prognosis, though some cases show early invasion, metastasis, and may become iodine-refractory. circRNAs can interact with miRNAs, bind proteins, regulate transcription, and encode polypeptides, but their translation function in thyroid cancer remains unexplored.

[METHODS] Quantitative real-time PCR (qRT-PCR), agarose gel electrophoresis, circRNA stability assessment, fluorescence in situ hybridization (FISH) were performed to explore the expression profile of circPTPRM in PTC tissues and adjacent non-cancerous thyroid tissues. We performed molecular biological and cell function experiments by constructing knockdown and various overexpression vectors. Effects of circPTPRM on PTC tumorigenesis were investigated through in vitro and in vivo experiments. The mechanism of circPTPRM-mediated tumor promotion was explored through immunofluorescence (IF), LC-MS/MS, immunoprecipitation (IP) and Co-immunoprecipitation (Co-IP), protein stability assessment, and ubiquitination assay.

[RESULTS] We confirmed that circPTPRM influenced PTC cell proliferation, migration, invasion through its translated polypeptides. In vivo experiments with nude mouse tumors also demonstrated that overexpression of circPTPRM contributed to the tumor's increased volume and weight. Subsequently, in the mechanistic analysis we found that circPTPRM-187aa polypeptide could bind IQGAP1 and induce TGF-β pathway activation by elevating RAC1 and CDC42.

[CONCLUSION] CircPTPRM can encode circPTPRM-187aa polypeptide. circPTPRM-187aa, regulates the expression of IQGAP1 protein, and up-regulates RAC1 and CDC42 proteins in TGF-β signaling pathway, enhancing the PTC cells proliferation, migration, and invasion.