A novel protein encoded by circUBE4B promotes progression of esophageal squamous cell carcinoma by augmenting MAPK/ERK signaling.

Esophageal squamous carcinoma (ESCC) is a common malignant cancer. Although the non-coding roles of circRNAs in the pathogenesis of human tumors have been well studied, whether circRNAs participate in the progression of ESCC by encoding novel proteins remains unclear. In this study, we identified an overexpression circRNA with protein-coding ability in ESCC tissues, called circUBE4B, whose expression level is correlated with tumor size and tumor differentiation level of ESCC patients. Moreover, a higher level of circUBE4B in ESCC patients is correlated with a worse prognosis. Functionally, we found that circUBE4B promoted the proliferation of ESCC cells by encoding a novel cancer-promoting protein, circUBE4B-173aa. Mechanistically, the circUBE4B-173aa protein interacts with MAPK1 and promotes the phosphorylation level of MAPK1 to eventually activate MAPK/ERK signaling pathway. The xenograft model revealed that overexpression of circUBE4B-173aa in ESCC cells significantly promoted the growth of grafts. Our study provides new insights into the mechanism of circRNA in the development of ESCC and circUBE4B-173aa has the potential to serve as a biomarker and a novel therapeutic target for ESCC therapy.