Circular RNAs (circRNAs) are a novel class of widespread noncoding RNAs that regulate gene expression in mammals. Recent studies demonstrate that functional peptides can be encoded by short open reading frames in noncoding RNAs, including circRNAs. However, the role of circRNAs in various physiological and pathological states, such as cancer, is 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 with matched paracancerous tissue. The hsa-circ-0000437 contains a short open reading frame 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 antitumor effects of CORO1C-47aa on EC progression suggest that CORO1C-47aa has potential value in anticarcinoma therapies and warrants further investigation.

中文翻译：

---

由环状非编码 RNA circ-0000437 编码的肽 CORO1C-47aa 在子宫内膜肿瘤血管生成中起负调节作用。

环状RNA（circRNA）是一类新型的广泛分布的非编码RNA，可调节哺乳动物的基因表达。最近的研究表明，功能性肽可以由非编码 RNA 中的短开放阅读框编码，包括 circRNA。然而，circRNAs在各种生理和病理状态中的作用，如癌症，尚不清楚。在本研究中，通过对人类子宫内膜癌 (EC) 样本及其配对的相邻正常组织进行深度 RNA 测序，我们发现与匹配的癌旁组织相比，EC 中的 circRNA hsa-circ-0000437 显着减少。hsa-circ-0000437 包含一个短的开放阅读框，编码称为 CORO1C-47aa 的功能性肽。CORO1C-47aa 的过表达能够通过与转录因子 TACC3 竞争结合 ARNT 并抑制 VEGF 来抑制内皮细胞增殖、迁移和分化，从而在起始阶段抑制血管生成。CORO1C-47aa 通过 PAS-B 结构域直接与 ARNT 结合，阻断 ARNT 与 TACC3 之间的关联，导致 VEGF 表达减少，最终导致血管生成减少。CORO1C-47aa 对 EC 进展的抗肿瘤作用表明 CORO1C-47aa 在抗癌治疗中具有潜在价值，值得进一步研究。这导致VEGF表达减少，最终导致血管生成减少。CORO1C-47aa 对 EC 进展的抗肿瘤作用表明 CORO1C-47aa 在抗癌治疗中具有潜在价值，值得进一步研究。这导致VEGF表达减少，最终导致血管生成减少。CORO1C-47aa 对 EC 进展的抗肿瘤作用表明 CORO1C-47aa 在抗癌治疗中具有潜在价值，值得进一步研究。