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新型环状 RNA circ_0086722 通过调控前列腺癌中的 miR-339-5p/STAT5A 轴促进肿瘤进展。

Novel circular RNA circ_0086722 drives tumor progression by regulating the miR-339-5p/STAT5A axis in prostate cancer.

机构信息

Department of Urology, The First Affiliated Hospital of Nanchang University, Yongwai street 17, Nanchang, 330000, China; Jiangxi Institute of Urology, Yongwai street 17, Nanchang, 330000, China.

Department of Urology, The First Affiliated Hospital of Nanchang University, Yongwai street 17, Nanchang, 330000, China; Jiangxi Institute of Urology, Yongwai street 17, Nanchang, 330000, China; Department of Urology, The First Hospital of Putian City, Putian, 351100, China.

出版信息

Cancer Lett. 2022 May 1;533:215606. doi: 10.1016/j.canlet.2022.215606. Epub 2022 Feb 25.

Abstract

Recent studies validate that circular RNAs have played critical regulatory functions in cancer biology. However, their contribution to prostate cancer (PCa) remained largely unclear. Our study aimed to explore the regulatory function and underlying mechanisms of circ_0086722 in PCa. The circ_0086722 levels in PCa tissues and cell lines were detected through qRT-PCR. In vivo and in vitro experiments were performed to evaluate the functions of circ_0086722 in PCa. Subsequently, the underlying mechanisms of circ_0086722 were explored with qRT-PCR, RNA immunoprecipitation, miRNA pull-down, and luciferase reporter assay experiments. Results revealed that circ_0086722 was highly expressed in PCa tissues and cell lines. Furthermore, high levels of circ_0086722 were positively correlated with pT3 stage, higher specimen Gleason score (>7), and worse biochemical recurrence-free survivals of PCa patients. Then, functional experiments revealed that circ_0086722 accelerated PCa proliferation and progression. Moreover, we demonstrated that circ_0086722 could mechanistically relieve the repressive effects of miR-339-5p on its target STAT5A, which facilitates PCa development. In conclusion, our findings revealed that circ_0086722 drives PCa development via the miR-339-5p/STAT5A axis, and it may function as a potential prognostic biomarker or therapeutic target for PCa treatment. Further studies with large sample sizes and sufficiently long follow-up periods are necessary to confirm the predictive role of circ_0086722 for the prognosis of PCa patients.

摘要

最近的研究证实,环状 RNA 在癌症生物学中发挥了关键的调控作用。然而,它们在前列腺癌(PCa)中的作用仍很大程度上不清楚。我们的研究旨在探讨 circ_0086722 在 PCa 中的调控功能和潜在机制。通过 qRT-PCR 检测 PCa 组织和细胞系中的 circ_0086722 水平。进行体内和体外实验以评估 circ_0086722 在 PCa 中的功能。随后,通过 qRT-PCR、RNA 免疫沉淀、miRNA 下拉和荧光素酶报告基因检测实验探索 circ_0086722 的潜在机制。结果表明,circ_0086722 在 PCa 组织和细胞系中高度表达。此外,高水平的 circ_0086722 与 pT3 期、更高的标本 Gleason 评分(>7)以及 PCa 患者更差的生化无复发生存率呈正相关。然后,功能实验表明 circ_0086722 加速了 PCa 的增殖和进展。此外,我们证明 circ_0086722 可以通过机制缓解 miR-339-5p 对其靶标 STAT5A 的抑制作用,从而促进 PCa 的发展。总之,我们的研究结果表明,circ_0086722 通过 miR-339-5p/STAT5A 轴驱动 PCa 的发展,它可能作为 PCa 治疗的潜在预后生物标志物或治疗靶点。需要进一步的大样本量和足够长的随访时间的研究来确认 circ_0086722 对 PCa 患者预后的预测作用。

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