Xu Weiqiang, Wu Yu, Zhang Guoxi
Suzhou Medical College, Soochow University, No.199 Ren'ai Road, Suzhou Industrial Park, 215000 Suzhou, Jiangsu Province China.
Department of Urology, The Second Affiliated Hospital of Bengbu Medical University, No. 633 Longhua Road, Huaishang District, 233000 Bengbu, Anhui Province China.
Cytotechnology. 2024 Apr;76(2):231-246. doi: 10.1007/s10616-023-00612-z. Epub 2024 Feb 14.
In several forms of malignant tumors, nuclear enriched abundant transcript 1 (NEAT1), a lncRNA, has been identified to play an important role. NEAT1's regulation patterns in prostate cancer (PCa) are, however, mainly unknown. This study was aimed to evaluate and study the roles and regulatory mechanisms of NEAT1 in PCa. NEAT1, miR-582-5p, and enhancer of zeste homolog 2 (EZH2) expression were detected by qRT-PCR. The PCa cells' invasive, migrative, and proliferative activities in vitro were assessed using transwell migration and invasion, wound-healing, cloning creation, and CCK-8 assays. In the present study, impaired proliferative, migrative, and invasive capacities were observed in the NEAT1-deficient PCa (PC3 and LNCaP) cells. Further mechanistic studies found that NEAT1 performs its function through sponging miR-582-5p. Furthermore, EZH2 was confirmed to be the downstream target gene of miRNA-582-5p. The impaired progression caused by NEAT1 deficiency in PCa cells was significantly restored by the inhibition of miR-582-5p, while these effects were largely abolished by the deletion of EZH2. Finally, the xenograft nude mouse model showed that knocking down the expression of NEAT1 suppressed the growth of PCa. In conclusion, NEAT1 promotes the progression of PCa by controlling the miR-582-5p and miR-582-5p-mediated EZH2.
The online version contains supplementary material available at 10.1007/s10616-023-00612-z.
在几种恶性肿瘤中,长链非编码RNA核富集丰富转录本1(NEAT1)已被证实发挥重要作用。然而,NEAT1在前列腺癌(PCa)中的调控模式主要尚不清楚。本研究旨在评估和研究NEAT1在PCa中的作用及调控机制。通过qRT-PCR检测NEAT1、miR-582-5p和zeste同源物2增强子(EZH2)的表达。使用Transwell迁移和侵袭、伤口愈合、克隆形成和CCK-8实验评估PCa细胞在体外的侵袭、迁移和增殖活性。在本研究中,在NEAT1缺陷的PCa(PC3和LNCaP)细胞中观察到增殖、迁移和侵袭能力受损。进一步的机制研究发现,NEAT1通过吸附miR-582-5p发挥其功能。此外,EZH2被证实是miRNA-582-5p的下游靶基因。抑制miR-582-5p可显著恢复NEAT1缺陷导致的PCa细胞进展受损,而缺失EZH2则在很大程度上消除了这些影响。最后,异种移植裸鼠模型显示,敲低NEAT1的表达可抑制PCa的生长。总之,NEAT1通过控制miR-582-5p及其介导的EZH2促进PCa的进展。
在线版本包含可在10.1007/s10616-023-00612-z获取的补充材料。