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Hsa_circ_0013561 promotes epithelial-mesenchymal transition and tumor progression by regulating ANXA2 via miR-23b-3p in ovarian cancer
Cancer Gene Therapy ( IF 6.4 ) Pub Date : 2023-12-15 , DOI: 10.1038/s41417-023-00686-z
Jia Lv , Yijun Zhang , Mengying Yang , Lianqiao Qiao , Huihui Wang , Huici Jiang , Mingxu Fu , Jinlong Qin , Shaohua Xu

Our preliminary experiment discovered that hsa_circ_0013561 was aberrantly expressed in OC. However, the underlying mechanism is unclear. The expression of hsa_circ_0013561 in OC cells and tissues was detected by RT-qPCR and fluorescence in situ hybridization. The effects of hsa_circ_0013561 on the proliferation and metastasis of OC were explored by functional experiments such as cell counting kit-8, transwell, and tumor xenograft models. To mechanistically understand the regulatory role of hsa_circ_0013561, bioinformatics analysis, Western blot, luciferase reporter assay, and a series of rescue experiments were applied. We found that the hsa_circ_0013561 expression was elevated in OC cells and tissues, and was correlated with metastasis formation. Downregulation of hsa_circ_0013561 suppressed the proliferation and migration of OC cells both in vitro and in vivo. Regarding the interactions of hsa_circ_0013561, the luciferase reporter assay verified that miR-23b-3p and Annexin A2 (ANXA2) were its downstream targets. MiR-23b-3p inhibition or ANXA2 overexpression reversed OC cell proliferation, migration, and epithelial-mesenchymal transition (EMT) post-hsa_circ_0013561 silencing. Moreover, ANXA2 overexpression also reversed OC cell migration, proliferation, and EMT after miR-23b-3p upregulation. Our data suggest that hsa_circ_0013561 increases the expression of ANXA2 by regulating miR-23b-3p competitively, resulting in EMT and metastasis of OC. Thus, hsa_circ_0013561 may serve as a novel oncogenic biomarker for OC progression.



中文翻译:


Hsa_circ_0013561 通过 miR-23b-3p 调节 ANXA2 促进卵巢癌上皮间质转化和肿瘤进展



我们的初步实验发现hsa_circ_0013561在OC中异常表达。然而,其根本机制尚不清楚。通过RT-qPCR和荧​​光原位杂交检测OC细胞和组织中hsa_circ_0013561的表达。通过细胞计数kit-8、Transwell、肿瘤异种移植模型等功能实验探讨hsa_circ_0013561对OC增殖和转移的影响。为了从机制上理解 hsa_circ_0013561 的调节作用,应用了生物信息学分析、蛋白质印迹、荧光素酶报告基因测定和一系列救援实验。我们发现 hsa_circ_0013561 表达在 OC 细胞和组织中升高,并且与转移形成相关。 hsa_circ_0013561 的下调抑制了 OC 细胞在体外和体内的增殖和迁移。关于 hsa_circ_0013561 的相互作用,荧光素酶报告基因检测证实 miR-23b-3p 和膜联蛋白 A2 (ANXA2) 是其下游靶标。 MiR-23b-3p 抑制或 ANXA2 过表达可逆转 hsa_circ_0013561 沉默后的 OC 细胞增殖、迁移和上皮间质转化 (EMT)。此外,ANXA2 过表达还可以逆转 miR-23b-3p 上调后的 OC 细胞迁移、增殖和 EMT。我们的数据表明 hsa_circ_0013561 通过竞争性调节 miR-23b-3p 增加 ANXA2 的表达,导致 EMT 和 OC 转移。因此,hsa_circ_0013561 可以作为 OC 进展的新型致癌生物标志物。

更新日期:2023-12-15
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