Circ_0001068通过抑制mir-149-5p活性促进FXYD5表达，从而加速卵巢癌的发展。

Circ_0001068 accelerates the development of ovarian cancer by promoting FXYD5 expression through inhibiting mir-149-5p activity.

作者信息

Mou Zhengqian, Ge Lingyan, Ye Saiya, Gong Zhiyong

机构信息

Obstetrics and Gynaecology Department, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, No.25, Nanmen Road, Chongming District, Shanghai, 202150, China.

Obstetrics and Gynaecology Department, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China.

出版信息

Discov Oncol. 2024 Nov 12;15(1):648. doi: 10.1007/s12672-024-01497-w.

DOI:10.1007/s12672-024-01497-w

PMID:39532790

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11557794/

Abstract

BACKGROUND

Ovarian cancer (OC) is one of the common malignancies of the female reproductive organs. Microarray analysis shows that circ_0001068 is upregulated in OC patients, however, its carcinogenic effect on OC development has not yet been revealed.

METHODS

In this study, qRT-PCR and western blotting were used to determine the expression of circ_0001068, microRNA-149-5p (miR-149-5p) and domain containing ion transport regulator 5 (FXYD5). Clone formation was used to assess cell proliferation, and transwell assays were performed to analyze cell migration and invasion. Dual-luciferase reporter and pull down assays were used to verify the binding relationship between circ_0001068 and miR-149-5p or FXYD5. Mouse xenograft tumor formation was performed to validate the role of circ_0001068 in vivo.

RESULTS

We found that the expression levels of circ_0001068 and FXYD5 were significantly increased in OC tissues and cell lines. Circ_0001068 knockdown significantly inhibited cell proliferation, migration, invasion, glycolysis, and glutamine metabolism. Circ_0001068 directly interacted with miR-149-5p, and the introduction of miR-149-5p mimics in OC cells partially reversed circ_0001068 knockdown-mediated effects. MiR-149-5p directly interacted with the 3'untranslated region (3'UTR) of FXYD5, and FXYD5 overexpression partially counteracted circ_0001068 knockdown-mediated effects in OC cells. Circ_0001068 knockdown inhibited xenograft tumor growth in vivo.

CONCLUSION

Our findings suggest that circ_0001068 promotes the malignant properties of OC cells by targeting the miR-149-5p/FXYD5 axis.

摘要

背景

卵巢癌（OC）是女性生殖器官常见的恶性肿瘤之一。微阵列分析显示，circ_0001068在OC患者中上调，然而，其对OC发生发展的致癌作用尚未揭示。

方法

在本研究中，采用qRT-PCR和蛋白质免疫印迹法检测circ_0001068、微小RNA-149-5p（miR-149-5p）和含离子转运调节域5（FXYD5）的表达。采用克隆形成实验评估细胞增殖，进行Transwell实验分析细胞迁移和侵袭。采用双荧光素酶报告基因实验和下拉实验验证circ_0001068与miR-149-5p或FXYD5之间的结合关系。进行小鼠异种移植瘤形成实验以验证circ_0001068在体内的作用。

结果

我们发现，circ_0001068和FXYD5的表达水平在OC组织和细胞系中显著升高。敲低circ_0001068显著抑制细胞增殖、迁移、侵袭、糖酵解和谷氨酰胺代谢。circ_0001068直接与miR-149-5p相互作用，在OC细胞中引入miR-149-5p模拟物可部分逆转敲低circ_0001068介导的效应。miR-149-5p直接与FXYD5的3'非翻译区（3'UTR）相互作用，FXYD5过表达可部分抵消敲低circ_0001068介导的OC细胞效应。敲低circ_0001068可抑制体内异种移植瘤的生长。