Department of Obstetrics and Gynecology, Northwest Women's and Children's Hospital, No. 1616, Yanxiang Road, Qujiang New District, Xi'an, 710061, China.
Mol Biotechnol. 2024 Sep;66(9):2522-2531. doi: 10.1007/s12033-023-00876-y. Epub 2023 Sep 25.
Endometrial cancer (EC) is the most common gynecological tumor. Circular RNAs are a novel type of non-coding RNA that have important regulatory functions, particularly in the pathogenic progression of cancer. In this study, we investigated the function of circCCL22, and elucidated its molecular mechanism in EC progresssion. The expression of circCCL22, miR-543 and CDC25A in EC tissues and cells were determined by qRT-PCR and western blot. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing and transwell assays were executed to assess the cell viability, proliferation, migration and invasion. Dual-luciferase report assay was utilized to investigate the interaction of miR-543 with circCCL22 and CDC25A. The role of circCCL22 in EC in vivo was investigated by xenograft assay. CircCCL22 was notably upregulated in EC tissues and cells. Functionally, circCCL22 knockdown suppressed EC cell proliferation, migration and invasion in vitro, and inhibited tumor growth in vivo. Mechanistically, circCCL22 acted as "miR-543 sponges" to regulate its targeted gene CDC25A expression in EC cells. The inhibiting effect induced by circCCL22 knockdown on EC cell proliferation, migration and invasion was greatly reversed by miR-543 inhibition or CDC25A overexpression. Our results revealed that circCCL22 regulated EC progression through targeting miR-543/CDC25A axis, and it could be a novel therapeutic target of EC.
子宫内膜癌（EC）是最常见的妇科肿瘤。环状 RNA 是一种新型的非编码 RNA，具有重要的调节功能，特别是在癌症的发病进展中。在这项研究中，我们研究了 circCCL22 的功能，并阐明了其在 EC 进展中的分子机制。通过 qRT-PCR 和 Western blot 检测 EC 组织和细胞中 circCCL22、miR-543 和 CDC25A 的表达。细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷、划痕愈合和 Transwell 测定用于评估细胞活力、增殖、迁移和侵袭。双荧光素酶报告实验用于研究 miR-543 与 circCCL22 和 CDC25A 的相互作用。通过异种移植实验研究 circCCL22 在 EC 体内的作用。circCCL22 在 EC 组织和细胞中明显上调。功能上，circCCL22 敲低抑制 EC 细胞在体外的增殖、迁移和侵袭，并抑制体内肿瘤生长。机制上，circCCL22 作为“miR-543 海绵”调节其在 EC 细胞中的靶基因 CDC25A 表达。circCCL22 敲低对 EC 细胞增殖、迁移和侵袭的抑制作用被 miR-543 抑制或 CDC25A 过表达大大逆转。我们的结果表明，circCCL22 通过靶向 miR-543/CDC25A 轴调节 EC 进展，它可能是 EC 的一种新的治疗靶点。
