Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu, China.
J Invest Surg. 2021 Sep;34(9):984-992. doi: 10.1080/08941939.2020.1738602. Epub 2020 Mar 13.
Growing evidence points at an association between microRNAs and tumor development. Although dysregulation of microRNA-103a-3p (miR-103a-3p) in multiple human cancers has been reported, its expression in prostate cancer (PCa) remains unknown and there is currently no research on the relationship between miR-103a-3p and tumor protein D52 (TPD52) in PCa. Our aim in this study was to explore the effect and potential mechanism of miR-103a-3p in PCa. qRT-PCR was performed to detected the level of miR-103a-3p in PCa tissues and cells, and in normal tissues. Colony, wound-healing, invasion, proliferation, and apoptosis assays were performed in search miR-103a-3p effect in PCa. TargetScan was used to predict potential targets of miR-103a-3p. Additionally, dual-luciferase reporter, western blot, and immunofluorescence assays were performed to detected the target gene of miR-103a-3p. Finally, we explore the differences in tumor xenograft experiments between nude mice injected with stably miR-103a-3p expressing cells and those expressing a miR-negative control. Low level of miR-103a-3p was detected in PCa tissues and cells, when compared with normal tissues. Enhancement of miR-103a-3p significantly inhibited migration and invasion of PCa cells, and negatively regulated expression of the oncogenic tumor protein D52 (TPD52) through direct binding to its 3'-UTR. Interestingly, overexpression of TPD52 significantly attenuated the effect of mir-103a-3p on PCa. Our study provides the first evidence that miR-103a-3p directly targets TPD52 and inhibits the proliferation and invasion of PCa. This finding helps clarify the role of mir-103a-3p-TPD52 axis in PCa and may provide new therapeutic targets for the disease.
越来越多的证据表明 microRNAs 与肿瘤的发生发展有关。尽管已有报道称 microRNA-103a-3p（miR-103a-3p）在多种人类癌症中失调，但在前列腺癌（PCa）中其表达情况尚不清楚，目前也没有研究 miR-103a-3p 与肿瘤蛋白 D52（TPD52）在 PCa 中的关系。本研究旨在探讨 miR-103a-3p 在 PCa 中的作用及其潜在机制。通过 qRT-PCR 检测 miR-103a-3p 在 PCa 组织和细胞以及正常组织中的水平。通过集落形成、划痕愈合、侵袭、增殖和凋亡实验研究 miR-103a-3p 在 PCa 中的作用。利用 TargetScan 预测 miR-103a-3p 的潜在靶标。此外，还进行了双荧光素酶报告、western blot 和免疫荧光实验，以检测 miR-103a-3p 的靶基因。最后，我们在裸鼠肿瘤异种移植实验中比较了稳定表达 miR-103a-3p 的细胞和表达 miR-阴性对照的细胞的肿瘤生长差异。与正常组织相比，PCa 组织和细胞中 miR-103a-3p 的水平较低。增强 miR-103a-3p 显著抑制 PCa 细胞的迁移和侵袭，并通过直接结合其 3'-UTR 负调控致癌肿瘤蛋白 D52（TPD52）的表达。有趣的是，TPD52 的过表达显著减弱了 mir-103a-3p 对 PCa 的作用。本研究首次证明 miR-103a-3p 可直接靶向 TPD52，并抑制 PCa 的增殖和侵袭。这一发现有助于阐明 mir-103a-3p-TPD52 轴在 PCa 中的作用，并为该疾病提供新的治疗靶点。
