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环状 RNA TENM3 通过 miR-558/RUNX3 轴抑制前列腺癌肿瘤进展。

CircTENM3 inhibites tumor progression via the miR-558/RUNX3 axis in prostate cancer.

机构信息

Department of Urinary Surgery, Suzhou Ninth People's Hospital, Soochow University, Suzhou, Jiangsu, China.

Department of Urology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China.

出版信息

J Transl Med. 2023 Nov 25;21(1):850. doi: 10.1186/s12967-023-04708-0.

Abstract

BACKGROUND

Prostate cancer (PCa) is currently acknowledged as the second most widespread cancer among men worldwide. Yet, the lack of dependable diagnostic biomarkers and therapeutic targets has presented considerable hurdles to the progression of prostate cancer treatment. Circular RNAs are implicated in the pathogenesis of numerous diseases, positioning them as promising biomarkers for diverse medical conditions. This study aims to uncover a specific circRNA that could serve as a diagnostic and therapeutic target for detecting and treating PCa.

METHODS

The change of circTENM3 expression levels in PCa was detected by qPCR. CCK8 assays, EdU assays, Scratch assay and Transwell migration assay conducted to detect the role of circTENM3 in PCa cells in vitro. RIP assay, RNA-pull down and luciferase reporter assay were performed to explore the mechanism of circTENM3. Gain-of-function analysis was performed to reveal the function of circTENM3 in PCa in vivo.

RESULTS

The results revealed that the expression level of circTENM3 was significantly down-regulated in PCa. CircTENM3 overexpression alleviated the progression of PCa in vitro. Mechanistically, circTENM3 enhanced RUNX3 levels via miR-558 sponge. Gain-of-function analysis determined that circTENM3 overexpression could inhibit PCa progression in vitro.

CONCLUSIONS

Our research offers profound insights into the protective role played by circTENM3 in PCa. CircTENM3 operates as a sponge for miR-558, thereby triggering the elevation of RUNX3 expression, which subsequently curbs the progression of PCa.

摘要

背景

前列腺癌(PCa)是目前全球男性第二大常见癌症。然而,缺乏可靠的诊断生物标志物和治疗靶点,给前列腺癌治疗的进展带来了相当大的障碍。环状 RNA 参与了许多疾病的发病机制,使其成为多种疾病有前途的生物标志物。本研究旨在发现一种特定的 circRNA,作为检测和治疗 PCa 的诊断和治疗靶点。

方法

通过 qPCR 检测 PCa 中 circTENM3 表达水平的变化。通过 CCK8 assays、EdU assays、Scratch assay 和 Transwell migration assay 检测 circTENM3 在体外 PCa 细胞中的作用。通过 RIP assay、RNA-pull down 和 luciferase reporter assay 探讨 circTENM3 的作用机制。通过 gain-of-function analysis 揭示 circTENM3 在体内 PCa 中的功能。

结果

结果表明,circTENM3 的表达水平在 PCa 中显著下调。circTENM3 的过表达可减轻 PCa 的体外进展。机制上,circTENM3 通过 miR-558 海绵增强 RUNX3 水平。功能获得分析确定 circTENM3 的过表达可抑制体外 PCa 的进展。

结论

我们的研究深入了解了 circTENM3 在 PCa 中发挥的保护作用。circTENM3 作为 miR-558 的海绵,从而触发 RUNX3 表达的升高,进而抑制 PCa 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2288/10675854/20a61b9ce22b/12967_2023_4708_Fig1_HTML.jpg

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