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环状RNA_0057558通过微小RNA-1238-3p/Septin 2轴加速前列腺癌的发展。

Circ_0057558 accelerates the development of prostate cancer through miR-1238-3p/SEPT2 axis.

作者信息

Yin Zhaofa, Zhang Ling, Liu Rong, Tong Liang, Jiang Chaoxiang, Kang Le

机构信息

Department of Urology, Loudi Central Hospital of Hunan Province, Loudi 417000, China.

Department of Urology, Loudi Central Hospital of Hunan Province, Loudi 417000, China.

出版信息

Pathol Res Pract. 2023 Mar;243:154317. doi: 10.1016/j.prp.2023.154317. Epub 2023 Jan 20.

DOI:10.1016/j.prp.2023.154317
PMID:36738516
Abstract

BACKGROUND

Prostate cancer (PCa) is one of the most common malignant tumors in males with high morbidity and mortality. Existing studies have demonstrated that circ_0057558 may be a molecular marker affecting PCa. However, its detailed roles in PCa remain unclear.

METHODS

The levels of circ_0057558, miR-1238-3p and Septin 2 (SEPT2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay, colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry assay, wound healing assay, transwell assay and tube formation assay were conducted for cell function identification. Xenograft tumor experiment was used to test the effect of circ_0057558 in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to determine the relationships between miR-1238-3p and circ_0057558 or SEPT2.

RESULTS

We identified that circ_0057558 level was elevated in PCa, and silencing circ_0057558 restrained PCa cell proliferation, survival, migration, invasion and angiogenesis. Circ_0057558 could sponge miR-1238-3p, and SEPT2 was the target of miR-1238-3p. Circ_0057558 promoted the expression of SEPT2 by negatively regulating miR-1238-3p, resulting in promotion of PCa progression. The effects of circ_0057558 knockdown in PCa development were overturned by the lack of miR-1238-3p. Also, overexpression of SEPT2 abolished the suppressive impacts of miR-1238-3p on PCa progression.

CONCLUSION

As a tumor promoter, circ_0057558 regulated the expression of miR-1238-3p and SEPT2 and facilitated PCa progression. These results indicated that circ_0057558 was a potential therapeutic marker of PCa.

摘要

背景

前列腺癌(PCa)是男性最常见的恶性肿瘤之一,发病率和死亡率都很高。现有研究表明,circ_0057558可能是影响前列腺癌的一个分子标志物。然而,其在前列腺癌中的具体作用仍不清楚。

方法

采用定量实时聚合酶链反应(qRT-PCR)检测circ_0057558、miR-1238-3p和Septin 2(SEPT2)的水平。通过细胞计数试剂盒-8(CCK-8)检测、集落形成检测、5-乙炔基-2'-脱氧尿苷(EdU)检测、流式细胞术检测、伤口愈合检测、Transwell检测和管腔形成检测来鉴定细胞功能。采用异种移植瘤实验来检测circ_0057558在体内的作用。进行双荧光素酶报告基因检测和RNA免疫沉淀(RIP)检测,以确定miR-1238-3p与circ_0057558或SEPT2之间的关系。

结果

我们发现前列腺癌中circ_0057558水平升高,沉默circ_0057558可抑制前列腺癌细胞的增殖、存活、迁移、侵袭和血管生成。Circ_0057558可以吸附miR-1238-3p,而SEPT2是miR-1238-3p的靶标。Circ_0057558通过负向调节miR-1238-3p促进SEPT2的表达,从而促进前列腺癌进展。miR-1238-3p的缺失推翻了circ_0057558敲低对前列腺癌发展的影响。此外,SEPT2的过表达消除了miR-1238-3p对前列腺癌进展的抑制作用。

结论

作为一种肿瘤促进因子,circ_0057558调节miR-1238-3p和SEPT2的表达,促进前列腺癌进展。这些结果表明circ_0057558是前列腺癌潜在的治疗标志物。

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