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miR-214-5p 通过调控 CRMP5 抑制人前列腺癌细胞的增殖和迁移。

miR-214-5p inhibits human prostate cancer proliferation and migration through regulating CRMP5.

机构信息

The Second Clinical Medical School (Zhujiang Hospital), Southern Medical University, Guangzhou, Guangdong, China.

Department of Urology, Zhujiang Hospital of Second Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China.

出版信息

Cancer Biomark. 2019;26(2):193-202. doi: 10.3233/CBM-190128.

DOI:10.3233/CBM-190128
PMID:31403941
Abstract

OBJECTIVES

In men, human prostate cancer (PCa) has become the second most common cancer. miRNAs are short non-coding RNAs that can inhibit target gene mRNAs. Studies have showed that the alternation of miRNAs expression in cancer is relevant to pathogenesis of tumor. In present study, we aimed to investigate functions of miR-214-5p in PCa.

MATERIALS AND METHODS

10 paired human prostate tumor tissues and homologous para-tumor tissues were recruited, and the levels of miR-214-5p and CRMP5 were respectively determined by qRT-PCR assay. Luciferase activity analysis was performed to explore the regulation of CRMP5 mRNA 3'UTR by miR-214-5p. Then, cell experiments, including cell proliferation, apoptosis, cell cycle, migration and colony formation ability, were performed after proper plasmids or RNAs transfection.

RESULTS

In PCa tissues and cell lines, expression of miR-214-5p was decreased compared with para-tumor tissues or normal prostate epithelial cell lines. Luciferase activity assay showed a direct combination of miR-214-5p and CRMP5 mRNA 3'UTR, and indicated that the absence of miR-214-5p in PCa cells may contributes to a high level of CRMP5. Cell experiments showed that miR-214-5p can induce inhibition of tumor cell growth, migration and colony forming efficiency, promotion of apoptosis and G1-phase arrest, on the other hand, co-expression of CRMP5 somewhat counteracted these phenotype induced by miR-214-5p.

CONCLUSION

Taken together, miR-214-5p shows tumor suppression effects in PCa cells. Loss expression of miR-214-5p in PCa increase levels of CRMP5 through regulating CRMP5 3'UTR, which could be a potential therapy target for PCa.

摘要

目的

在男性中,前列腺癌(PCa)已成为第二大常见癌症。miRNA 是一种短的非编码 RNA,可以抑制靶基因 mRNA。研究表明,miRNA 表达的改变与肿瘤的发病机制有关。在本研究中,我们旨在研究 miR-214-5p 在 PCa 中的功能。

材料和方法

招募了 10 对人前列腺癌组织和同源癌旁组织,通过 qRT-PCR 检测 miR-214-5p 和 CRMP5 的水平。通过荧光素酶活性分析研究 miR-214-5p 对 CRMP5 mRNA 3'UTR 的调节作用。然后,进行适当的质粒或 RNA 转染后,进行细胞实验,包括细胞增殖、凋亡、细胞周期、迁移和集落形成能力。

结果

在 PCa 组织和细胞系中,miR-214-5p 的表达低于癌旁组织或正常前列腺上皮细胞系。荧光素酶活性测定显示 miR-214-5p 与 CRMP5 mRNA 3'UTR 直接结合,并表明 PCa 细胞中 miR-214-5p 的缺失可能导致 CRMP5 水平升高。细胞实验表明,miR-214-5p 可诱导肿瘤细胞生长、迁移和集落形成效率的抑制,促进凋亡和 G1 期阻滞,另一方面,CRMP5 的共表达在一定程度上抵消了 miR-214-5p 诱导的这些表型。

结论

综上所述,miR-214-5p 在 PCa 细胞中表现出肿瘤抑制作用。PCa 中 miR-214-5p 的缺失通过调节 CRMP5 3'UTR 增加 CRMP5 的水平,这可能是 PCa 的潜在治疗靶点。

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