环状 RNA 0025033 通过靶向 miR-184 激活 LSM4 的表达促进卵巢癌细胞的进展。

Circ_0025033 promotes the progression of ovarian cancer by activating the expression of LSM4 via targeting miR-184.

机构信息

Department of Gynecology and Obstetrics, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China.

出版信息

Pathol Res Pract. 2021 Jan;217:153275. doi: 10.1016/j.prp.2020.153275. Epub 2020 Nov 17.

DOI:10.1016/j.prp.2020.153275

PMID:33285422

Abstract

BACKGROUND

Ovarian cancer (OC) is the leading disorder to threaten women's lives. Numerous circular RNAs (circRNAs) were identified in cancers with dysregulation and involved in the pathogenesis of cancer. This study investigated the function and regulatory mechanism of circ_0025033 in OC development, aiming to provide a potential strategy for OC treatment.

METHODS

For expression analysis, the expression levels of circ_0025033, LSM4 mRNA and miR-184 were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein level of LSM4 expression was detected by western blot. For functional analysis, the capacities of colony formation, migration/invasion and glycolysis metabolism were assessed by colony formation assay, transwell assay and the levels of glucose consumption and lactate production. The interaction between miR-184 and circ_0025033 or LSM4 was predicted by the bioinformatics tool and validated by dual-luciferase reporter assay. Xenograft models were established to determine the role of circ_0025033 in vivo.

RESULTS

The expression of circ_0025033 and LSM4 was promoted in OC tissues and cells. Circ_0025033 knockdown or LSM4 knockdown blocked the ability of colony formation, migration/invasion and glycolysis metabolism in OC cells. In mechanism, circ_0025033 functioned as a "competing endogenous RNA (ceRNA)" to modulate LSM4 expression by targeting miR-184. LSM4 overexpression recovered the inhibitory effects on colony formation, migration/invasion and glycolysis metabolism caused by circ_0025033 knockdown. Moreover, circ_0025033 knockdown also inhibited tumor growth in vivo by regulating LSM4 and targeting miR-184.

CONCLUSION

Circ_0025033 promotes the progression of OC by regulating LSM4 expression via targeting miR-184, which provided a new strategy to treat OC.

摘要

背景

卵巢癌（OC）是威胁女性生命的主要疾病。大量的环状 RNA（circRNA）在失调的癌症中被鉴定出来，并参与了癌症的发病机制。本研究旨在探讨 circ_0025033 在 OC 发展中的功能和调控机制，为 OC 治疗提供潜在策略。

方法

为了进行表达分析，通过实时定量聚合酶链反应（qRT-PCR）检测 circ_0025033、LSM4 mRNA 和 miR-184 的表达水平，并通过 Western blot 检测 LSM4 表达的蛋白水平。为了进行功能分析，通过集落形成实验、Transwell 实验和葡萄糖消耗和乳酸产生水平评估集落形成、迁移/侵袭和糖酵解代谢能力。通过生物信息学工具预测 miR-184 与 circ_0025033 或 LSM4 的相互作用，并通过双荧光素酶报告基因实验进行验证。建立异种移植模型以确定 circ_0025033 在体内的作用。

结果

circ_0025033 和 LSM4 的表达在 OC 组织和细胞中被促进。circ_0025033 敲低或 LSM4 敲低阻断了 OC 细胞的集落形成、迁移/侵袭和糖酵解代谢能力。在机制上，circ_0025033 通过靶向 miR-184 作为“竞争内源性 RNA（ceRNA）”来调节 LSM4 表达。LSM4 的过表达恢复了 circ_0025033 敲低引起的集落形成、迁移/侵袭和糖酵解代谢的抑制作用。此外，circ_0025033 敲低通过调节 LSM4 和靶向 miR-184 也抑制了体内肿瘤的生长。