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环状 RNA circANKS1B 作为 miR-152-3p 的海绵体,通过上调 TGF-α 的表达促进前列腺癌的进展。

Circular RNA circANKS1B acts as a sponge for miR-152-3p and promotes prostate cancer progression by upregulating TGF-α expression.

机构信息

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Institute of Urology, Anhui Medical University, Hefei, Anhui, China.

出版信息

Prostate. 2021 Apr;81(5):271-278. doi: 10.1002/pros.24102. Epub 2021 Feb 8.

DOI:10.1002/pros.24102
PMID:33556191
Abstract

BACKGROUND

A growing number of studies indicate that circular RNAs (circRNAs) play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aimed to investigate the expression and function of circANKS1B in prostate cancer (PC).

METHODS

The expression of circANKS1B and miR-152-3p was analyzed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell migration and invasion were measured using a transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by a dual-luciferase reporter gene assay. Rescue experiments were conducted to determine whether circANKS1B regulated the invasion of PC cells via the circANKS1B-miR-152-3p-TGF-α pathway.

RESULTS

The expression of circANKS1B was markedly upregulated in both PC cells and tissues. Moreover, high circANKS1B expression was associated with poor prognosis in PC patients. Dual-luciferase reporter assay indicated that circANKS1B directly bound to miR-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B markedly suppressed cell migration and invasion and TGF-α expression in PC cells, whereas the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on invasion of circANKS1B-deficient PC cells was also abrogated by TGF-α deficiency. Overall, circANKS1B acts as a sponge for miR-152-3p to promote PC progression by upregulating TGF-α expression.

CONCLUSION

Our findings reveal that circANKS1B may be a potential prognostic biomarker and therapeutic target for PC.

摘要

背景

越来越多的研究表明,环状 RNA(circRNAs)在人类疾病中发挥着关键作用,并具有作为生物标志物和治疗靶点的巨大潜力。本研究旨在探讨 circANKS1B 在前列腺癌(PC)中的表达和功能。

方法

通过实时定量逆转录聚合酶链反应(qRT-PCR)分析 circANKS1B 和 miR-152-3p 的表达。使用 Transwell 测定法测量细胞迁移和侵袭。通过双荧光素酶报告基因测定法证实 circANKS1B 和 miR-152-3p 之间的相互作用。进行挽救实验以确定 circANKS1B 是否通过 circANKS1B-miR-152-3p-TGF-α 通路调节 PC 细胞的侵袭。

结果

circANKS1B 在 PC 细胞和组织中均明显上调。此外,circANKS1B 高表达与 PC 患者的预后不良相关。双荧光素酶报告基因测定表明,circANKS1B 直接与 miR-152-3p 结合。此外,circANKS1B 负调控 miR-152-3p 的表达。circANKS1B 敲低显着抑制 PC 细胞的迁移和侵袭以及 TGF-α 的表达,而 miR-152-3p 缺陷则逆转了 circANKS1B 沉默的作用。此外,TGF-α 缺陷也消除了 miR-152-3p 沉默对 circANKS1B 缺陷 PC 细胞侵袭的影响。总之,circANKS1B 通过上调 TGF-α 的表达作为 miR-152-3p 的海绵促进 PC 的进展。

结论

我们的研究结果表明,circANKS1B 可能是 PC 的潜在预后生物标志物和治疗靶标。

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