Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region (Ministry of Education), College of Life Sciences, Guizhou University, Guiyang, Guizhou 550025, P.R. China.
Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, P.R. China.
Int J Oncol. 2023 Jan;62(1). doi: 10.3892/ijo.2022.5464. Epub 2022 Dec 9.
Prostate cancer (PCa) is one of the most fundamental causes of cancer‑related mortality and morbidity among males. However, the underlying mechanisms have not yet been fully clarified. The present study aimed to investigate the effects of plasmacytoma variant translocation 1 (PVT1) on the malignant behaviors of PCa cells and to explore the possible molecular mechanisms involved. The expression levels of PVT1 and microRNA (miRNA/miR)‑27b‑3p in PCa tissues and cell lines were measured using reverse‑transcritpion‑quantitative polymerase chain reaction. Methyltransferase 3 (METTL3)‑mediated PVT1 N‑methyladenosine (mA) modifications were detected using RNA immunoprecipitation (RIP) and RNA pull‑down assays. Bioinformatics analysis was used to predict the interactions of miR‑27b‑3p with PVT1 and bloom syndrome protein (BLM), and these interactions were validated using RIP, dual‑luciferase reporter and biotin pull‑down assays. The functional importance of miR‑27b‑3p, PVT1 and BLM within PCa cells was assessed through the utilization of Cell Counting Kit‑8, Transwell, wound healing and colony formation assays, and the use of a mouse xenograft model. The results revealed the high expression level of PVT1 in PCa tissues and cells, and epigenetic analyses revealed the upregulation of PVT1 expression following METTL3‑mediated mA modification. PVT1 overexpression induced PCa cells to become more proliferative, migratory and invasive, whereas PVT1 knockdown led to the opposite phenotype. Furthermore, miR‑27b‑3p was found to target both PVT1 and BLM, and PVT1 functioned to sequester miR‑27b‑3p within cells, thereby indirectly promoting the BLM expression level. BLM overexpression reversed the adverse effects of PVT1 knockdown on the migratory, proliferative and invasive capabilities of PCa cells and . The overexpression of PVT1 contributed to the aggressive phenotype of PCa cells by regulating the miR‑27b‑3p/BLM axis. On the whole, the findings of the present study may provide novel potential targets for the treatment of PCa.
前列腺癌 (PCa) 是男性癌症相关死亡率和发病率的最基本原因之一。然而，其潜在机制尚未完全阐明。本研究旨在探讨浆细胞瘤变异易位 1 (PVT1) 对 PCa 细胞恶性行为的影响，并探讨涉及的可能分子机制。采用逆转录定量聚合酶链反应检测 PCa 组织和细胞系中 PVT1 和 microRNA (miRNA/miR)-27b-3p 的表达水平。采用 RNA 免疫沉淀 (RIP) 和 RNA 下拉实验检测甲基转移酶 3 (METTL3) 介导的 PVT1 N6-甲基腺苷 (mA) 修饰。通过 RIP、双荧光素酶报告基因和生物素下拉实验验证 miR-27b-3p 与 PVT1 和布卢姆综合征蛋白 (BLM) 的相互作用的生物信息学分析。通过使用细胞计数试剂盒-8、Transwell、划痕愈合和集落形成实验以及小鼠异种移植模型评估 miR-27b-3p、PVT1 和 BLM 在 PCa 细胞中的功能重要性。结果显示，PVT1 在 PCa 组织和细胞中表达水平较高，表观遗传学分析显示，METTL3 介导的 mA 修饰后 PVT1 表达上调。PVT1 过表达诱导 PCa 细胞增殖、迁移和侵袭能力增强，而 PVT1 敲低则导致相反的表型。此外，发现 miR-27b-3p 靶向 PVT1 和 BLM，PVT1 功能将 miR-27b-3p 隔离在细胞内，从而间接促进 BLM 表达水平。BLM 过表达逆转了 PVT1 敲低对 PCa 细胞迁移、增殖和侵袭能力的不利影响。PVT1 的过表达通过调节 miR-27b-3p/BLM 轴促进 PCa 细胞的侵袭表型。总的来说，本研究的结果可为治疗 PCa 提供新的潜在靶点。
