环状 RNA LMTK2 通过调控 microRNA-183 的表达在前列腺癌中发挥抑癌作用。

CircLMTK2 acts as a tumor suppressor in prostate cancer via regulating the expression of microRNA-183.

机构信息

Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin150001, China.

Department of Reproductive Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin150001, China.

出版信息

Life Sci. 2020 Jan 15;241:117097. doi: 10.1016/j.lfs.2019.117097. Epub 2019 Nov 21.

DOI:10.1016/j.lfs.2019.117097

PMID:31760099

Abstract

BACKGROUND

Prostate cancer (PCa) is one of the commonest male urinary and reproductive system malignancies with high morbidity and mortality. circLMTK2 was reported as a tumor suppressor, therefore, we attempted to investigate the potential mechanism of circLMTK2 in PCa.

METHODS

qRT-PCR was employed to examine the expressions of circLMTK2 and miR-183. Afterwards, cell transfection was conducted for overexpressing circLMTK2 and miR-183 in LNCaP and PC3 cells, and silencing circLMTK2 in RWPE1 cells. Then, CCK-8 assay, BrdU, transwell assay, flow cytometry and western blot were respectively conducted to examine the variations of cell growth and metastasis, as well as apoptosis. The expressions of key proteins involved in Wnt/β-catenin and PI3K/AKT pathways were further investigated utilizing western blot.

RESULTS

circLMTK2 was lowly expressed in tumor tissues. circLMTK2 overexpression suppressed cell proliferation and metastasis, however promoted cell apoptosis in LNCaP and PC3 cells. circLMTK2 knockdown enhanced cell viability, proliferation, migration and invasion, while had no significant influences on apoptosis of RWPE1 cells. Further experiments verified that miR-183 up-regulation counteracted the influences triggered by circLMTK2 overexpression in LNCaP and PC3 cells. Besides, it markedly promoted the viability, proliferation, migration and invasion of LNCaP cells, however had no significant influence on cell apoptosis. Moreover, the inhibitory effects on Wnt/β-catenin and PI3K/AKT pathways evoked by circLMTK2 overexpression were diminished by miR-183 up-regulation in LNCaP and PC3 cells.

CONCLUSION

These outcomes illustrated that circLMTK2 overexpression exerts an anti-tumor effects through down-regulating the expression of miR-183.

摘要

背景

前列腺癌（PCa）是男性泌尿系统和生殖系统最常见的恶性肿瘤之一，发病率和死亡率都很高。circLMTK2 被报道为一种肿瘤抑制因子，因此，我们试图研究 circLMTK2 在 PCa 中的潜在机制。

方法

采用 qRT-PCR 检测 circLMTK2 和 miR-183 的表达。然后，通过转染在 LNCaP 和 PC3 细胞中转染过表达 circLMTK2 和 miR-183，并在 RWPE1 细胞中沉默 circLMTK2。然后，分别采用 CCK-8 法、BrdU 法、Transwell 法、流式细胞术和 Western blot 检测细胞生长和转移以及细胞凋亡的变化。进一步利用 Western blot 检测涉及 Wnt/β-catenin 和 PI3K/AKT 通路的关键蛋白的表达。

结果

circLMTK2 在肿瘤组织中低表达。circLMTK2 的过表达抑制了 LNCaP 和 PC3 细胞的增殖和转移，但促进了细胞凋亡。circLMTK2 的敲低增强了 RWPE1 细胞的活力、增殖、迁移和侵袭，但对细胞凋亡没有显著影响。进一步的实验验证了 miR-183 的上调逆转了 circLMTK2 过表达在 LNCaP 和 PC3 细胞中引发的变化。此外，它显著促进了 LNCaP 细胞的活力、增殖、迁移和侵袭，但对细胞凋亡没有显著影响。此外，circLMTK2 过表达对 LNCaP 和 PC3 细胞中 Wnt/β-catenin 和 PI3K/AKT 通路的抑制作用被 miR-183 的上调所减弱。