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微小 RNA miR-145-5p 通过抑制磷酸脂酶 D5(PLD5)下调细胞增殖和转移,从而减轻前列腺癌。

MicroRNA miR-145-5p inhibits Phospholipase D 5 (PLD5) to downregulate cell proliferation and metastasis to mitigate prostate cancer.

机构信息

Department of Oncology, NO.215 Hospital of shaanXi Nuclear Industry, Xianyang City, Shanxi Province, China.

Department of Urology, NO.215 Hospital of shaanXi Nuclear Industry, Xianyang City, Shanxi Province, China.

出版信息

Bioengineered. 2021 Dec;12(1):3240-3251. doi: 10.1080/21655979.2021.1945361.

DOI:10.1080/21655979.2021.1945361
PMID:34238129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8806496/
Abstract

Prostate cancer (PCa), a frequently detected malignant tumor, is the fifth leading global cancer mortality cause in men. Although research has improved the PCa survival rate, significantly reduced survival occurs among patients at the metastatic stage. MiRNAs, which are short non-coding proteins, are crucial for several biological roles, essential for PCa proliferation, differentiation, multiplication, and migration. The investigation aimed to explore miR-145-5p and PLD5 association and clarify their function in regulating proliferation in PCa cell lines.The study used PC-3, LNCaP, DU-145 PCa, and RWPE-1 non-cancerous cell line, PCa, and BPH tissue specimens, and nude mice to validate results. MiR-145-5p and PLD5 manifestation were assessed through RT-qPCR. PLD5 and miR-145 binding was determined through dual-luciferase reporter gene assays. Validation of cell proliferation, migration, and invasion was assessed through MTT, scratch wound, and transwell assays, respectively.The results indicated a downregulation of miR-145-5p level in PCa cell lines and tissues in comparison to the non-cancerous controls. PLD5 overexpression exerted a cancerous effect while mimicking of miR-145-5p reversed the PLD5-oncogenic effects and significantly inhibited PCa cells proliferation, migration, invasion, and metastasis.In conclusion, the study revealed that miR-145-5p upregulated apoptosis and repressed migration, invasion, and metastasis of PCa via direct PLD5 modulation.

摘要

前列腺癌(PCa)是一种常见的恶性肿瘤,是全球男性第五大癌症死亡原因。虽然研究提高了 PCa 的生存率,但转移性阶段的患者生存率仍然显著降低。miRNA 是一种短的非编码蛋白,在许多生物学功能中起着至关重要的作用,对 PCa 的增殖、分化、增殖和迁移都必不可少。本研究旨在探讨 miR-145-5p 与 PLD5 的关联,并阐明其在调节 PCa 细胞系增殖中的作用。

该研究使用了 PC-3、LNCaP、DU-145 PCa 和 RWPE-1 非癌性细胞系、PCa 和 BPH 组织标本以及裸鼠来验证结果。通过 RT-qPCR 评估 miR-145-5p 和 PLD5 的表达。通过双荧光素酶报告基因实验确定 PLD5 和 miR-145 的结合。通过 MTT、划痕实验和 Transwell 实验分别评估细胞增殖、迁移和侵袭的验证。

结果表明,与非癌对照相比,PCa 细胞系和组织中的 miR-145-5p 水平下调。PLD5 的过表达表现出致癌作用,而 miR-145-5p 的模拟则逆转了 PLD5 的致癌作用,并显著抑制了 PCa 细胞的增殖、迁移、侵袭和转移。

综上所述,该研究表明,miR-145-5p 通过直接调节 PLD5 来上调凋亡并抑制 PCa 的迁移、侵袭和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f72/8806496/3580c9ee7094/KBIE_A_1945361_F0006_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f72/8806496/c515f0c70706/KBIE_A_1945361_F0001_B.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f72/8806496/3580c9ee7094/KBIE_A_1945361_F0006_OC.jpg

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