Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277# Jiefang Avenue, Wuhan, 430022, Hubei, People's Republic of China.
J Transl Med. 2022 Mar 22;20(1):139. doi: 10.1186/s12967-022-03334-6.
Metastasis is critical for endometrial cancer (EC) progression and prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) can operate as independent functional entities. However, the functional regulatory mechanisms of circRNAs in EC remain unclear.
The levels of circESRP1, miR-874-3p, and CPEB4 mRNA in EC tissues and cells were determined by qRT-PCR. Sanger sequencing, PCR with divergent primers, an actinomycin D assay, and RNase R treatment were applied to verify the circular properties. Fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic fractionation were used to determine the localization of circESRP1. CCK-8, EdU incorporation, colony formation, Transwell, and wound healing assays were applied to assess the effects of circESRP1 on cell proliferation, migration, and invasion. The mutual regulatory mechanism of ceRNAs was investigated using dual-luciferase reporter, RNA pulldown, RNA immunoprecipitation (RIP), and Western blot assays. The biological effects were further validated in vivo in nude mouse xenograft models.
circESRP1 was highly expressed in EC tissues and cells and was mainly localized in the cytoplasm. Silencing circESRP1 inhibited the proliferation, migration, and invasion of EC cells in vitro and in vivo; however, overexpression of circESRP1 had the opposite effects. Mechanistically, circESRP1 sponged miR-874-3p to upregulate CPEB4 expression and ultimately contribute to EC cell proliferation and metastasis. Furthermore, circESRP1 regulated tumour growth in xenograft models.
CircESRP1 can interact with miR-874-3p to regulate EMT in endometrial cancer via the miR-874-3p/CPEB4 axis. CircESRP1 may serve as a promising therapeutic target for endometrial cancer.
转移是子宫内膜癌（EC）进展和预后的关键。越来越多的证据表明，环状 RNA（circRNA）可以作为独立的功能实体发挥作用。然而，circRNA 在 EC 中的功能调控机制尚不清楚。
采用 qRT-PCR 检测 EC 组织和细胞中 circESRP1、miR-874-3p 和 CPEB4 mRNA 的水平。采用 Sanger 测序、用分歧引物进行 PCR、放线菌素 D 测定和 RNase R 处理来验证 circRNA 的环状特性。应用荧光原位杂交（FISH）和核质分离来确定 circESRP1 的定位。采用 CCK-8、EdU 掺入、集落形成、Transwell 和划痕愈合实验来评估 circESRP1 对细胞增殖、迁移和侵袭的影响。采用双荧光素酶报告基因、RNA 下拉、RNA 免疫沉淀（RIP）和 Western blot 实验来研究 ceRNA 的相互调控机制。并在裸鼠异种移植模型中进一步验证了其生物学效应。
circESRP1 在 EC 组织和细胞中高表达，主要定位于细胞质。沉默 circESRP1 抑制 EC 细胞在体外和体内的增殖、迁移和侵袭；而过表达 circESRP1 则产生相反的效果。机制上，circESRP1 可以吸附 miR-874-3p，上调 CPEB4 的表达，最终促进 EC 细胞的增殖和转移。此外，circESRP1 调节了异种移植模型中的肿瘤生长。
circESRP1 可以通过 circESRP1/miR-874-3p/CPEB4 轴与 miR-874-3p 相互作用，调节子宫内膜癌中的 EMT。circESRP1 可能成为子宫内膜癌有前途的治疗靶点。
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