PGM5-AS1 抑制 miR-587 介导的 GDF10 抑制作用并破坏前列腺癌的进展。

PGM5-AS1 impairs miR-587-mediated GDF10 inhibition and abrogates progression of prostate cancer.

机构信息

Department of Oncology, Linyi People's Hospital, No. 27, East Section of Jiefang RoadShandong, Linyi, 276000, People's Republic of China.

出版信息

J Transl Med. 2021 Jan 6;19(1):12. doi: 10.1186/s12967-020-02572-w.

BACKGROUND

Prostate cancer (PCa) is a leading cause of cancer-related death in males. Aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in various human malignancies, including PCa. This study aims to clarify the inhibitory role of human PGM5 antisense RNA 1 (PGM5-AS1) in the proliferation and apoptosis of PCa cells.

METHODS

The regulatory network of PGM5-AS1/microRNA-587 (miR-587)/growth and differentiation factor 10 (GDF10) axis was examined by dual-luciferase reporter gene assay, RNA-binding protein immunoprecipitation, and RNA pull down assay. We manipulated the expression of PGM5-AS1, miR-587 and GDF10 by transducing expression vectors, mimic, inhibitor, or short hairpin RNA into PCa cells, thus establishing their functions in cell proliferation and apoptosis. Additionally, we measured the tumorigenicity of PCa cells xenografted in nude mice.

RESULTS

PGM5-AS1 is expressed at low levels in PCa cell lines. Forced overexpression of PGM5-AS1 restricted proliferation and facilitated apoptosis of PCa cells, manifesting in suppressed xenograft tumor growth in nude mice. Notably, PGM5-AS1 competitively bound to miR-587, which directly targets GDF10. We further validated that the anti-cancer role of PGM5-AS1 in PCa cells was achieved by binding to miR-587 to promote the expression of GDF10.

CONCLUSION

PGM5-AS1 upregulates GDF10 gene expression by competitively binding to miR-587, thus inhibiting proliferation and accelerating apoptosis of PCa cells.

背景

前列腺癌（PCa）是男性癌症相关死亡的主要原因。长链非编码 RNA（lncRNA）的异常表达与包括 PCa 在内的多种人类恶性肿瘤有关。本研究旨在阐明人 PGM5 反义 RNA 1（PGM5-AS1）在 PCa 细胞增殖和凋亡中的抑制作用。

方法

通过双荧光素酶报告基因检测、RNA 结合蛋白免疫沉淀和 RNA 下拉实验检测 PGM5-AS1/miR-587（miR-587）/生长分化因子 10（GDF10）轴的调控网络。通过转染表达载体、模拟物、抑制剂或短发夹 RNA 来操纵 PGM5-AS1、miR-587 和 GDF10 的表达，从而研究它们在细胞增殖和凋亡中的功能。此外，我们还测量了 PGM5-AS1 转染的裸鼠异种移植 PCa 细胞的致瘤性。

结果

PGM5-AS1 在 PCa 细胞系中低表达。强制过表达 PGM5-AS1 可限制 PCa 细胞的增殖并促进其凋亡，从而抑制裸鼠异种移植肿瘤的生长。值得注意的是，PGM5-AS1 与 miR-587 竞争结合，miR-587 可直接靶向 GDF10。我们进一步验证了 PGM5-AS1 通过与 miR-587 结合促进 GDF10 的表达，从而在 PCa 细胞中发挥抗癌作用。