A peptide CORO1C-47aa encoded by the circular non-coding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis.

Circular RNAs (circRNA) are a novel class of widespread non-coding RNAs (ncRNAs) that regulate gene expression in mammals. Recent studies demonstrate that functional peptides can be encoded by short open reading frames (sORFs) in ncRNAs, including circRNAs. However, the role of circRNAs in various physiological and pathological states, such as cancer, are not well understood. In this study, through deep RNA sequencing on human endometrial cancer (EC) samples and their paired adjacent normal tissues, we uncovered that the circRNA hsa-circ-0000437 is significantly reduced in EC compared to matched paracancerous tissue. The hsa-circ-0000437 contains a sORF encoding a functional peptide termed CORO1C-47aa. Overexpression of CORO1C-47aa is capable of inhibiting angiogenesis at the initiation stage by suppressing endothelial cell proliferation, migration, and differentiation through competition with transcription factor TACC3 to bind to ARNT and suppress VEGF. CORO1C-47aa directly bound to ARNT through the PAS-B domain and blocking the association between ARNT and TACC3 which led to reduced expression of VEGF ultimately lead to reduced angiogenesis. The anti-tumor effects of CORO1C-47aa on EC progression suggest that CORO1C-47aa has potential value in anti-carcinoma therapies and warrants further investigation.