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miRNA-215-5p 通过靶向 PGK1 缓解前列腺癌的转移。

MiRNA-215-5p alleviates the metastasis of prostate cancer by targeting PGK1.

机构信息

Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Jan;24(2):639-646. doi: 10.26355/eurrev_202001_20040.

DOI:10.26355/eurrev_202001_20040
PMID:32017004
Abstract

OBJECTIVE

MicroRNAs (miRNAs) are endogenous, non-coding RNAs, which exert crucial functions in regulating biological progressions. Previous studies have demonstrated the anti-tumor effect of miRNA-215-5p. However, its specific role in influencing the progression of prostate cancer (PCa) remains unclear. This study aims to uncover the regulatory effect of miRNA-215-5p on the metastasis and prognosis of PCa.

PATIENTS AND METHODS

MiRNA-215-5p levels in collected PCa tissues (n=52) and paracancerous tissues (n=52) were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between miRNA-215-5p level and pathological indexes, as well as overall survival of PCa patients, was analyzed. Regulatory effects of miRNA-215-5p on proliferative and metastatic capacities of LNCaP and DU-145 cells were evaluated through cell counting kit-8 (CCK-8) and transwell assay, respectively. Bioinformatics prediction was performed to search for the target genes of miRNA-215-5p and PGK1 was selected. The biological role of PGK1 in the progression of PCa was finally clarified by a series of rescue experiments.

RESULTS

MiRNA-215-5p was lowly expressed in PCa tissues and cell lines. Low level of miRNA-215-5p predicted poor prognosis in PCa patients. The silence of miRNA-215-5p enhanced viability, migratory, and invasive capacities of LNCaP cells, while the overexpression of miRNA-215-5p yielded the opposite trends in DU-145 cells. PGK1 was predicted to be the target of miRNA-215-5p. PGK1 was upregulated in PCa tissues and cell lines and its high level predicted poor prognosis of PCa. Moreover, PGK1 level was negatively correlated to that of miRNA-215-5p in PCa tissues. PGK1 was able to reverse the regulatory effects of miRNA-215-5p on metastatic potentials of PCa cells.

CONCLUSIONS

Downregulated miRNA-215-5p in PCa is closely related to distant metastasis and poor prognosis of affected patients. MiRNA-215-5p alleviates the malignant progression of PCa by targeting and downregulating PGK1.

摘要

目的

微小 RNA(miRNAs)是内源性的非编码 RNA,在调控生物进程中发挥着关键作用。已有研究表明 miRNA-215-5p 具有抗肿瘤作用。然而,其影响前列腺癌(PCa)进展的具体作用尚不清楚。本研究旨在揭示 miRNA-215-5p 对 PCa 转移和预后的调控作用。

患者与方法

采用实时定量聚合酶链反应(qRT-PCR)检测 52 例 PCa 组织和 52 例癌旁组织中 miRNA-215-5p 的水平。分析 miRNA-215-5p 水平与 PCa 患者病理指标及总生存期的关系。通过细胞计数试剂盒-8(CCK-8)和 Transwell 实验分别评估 miRNA-215-5p 对 LNCaP 和 DU-145 细胞增殖和转移能力的调控作用。通过生物信息学预测寻找 miRNA-215-5p 的靶基因,并选择 PGK1。通过一系列挽救实验最终阐明 PGK1 在 PCa 进展中的生物学作用。

结果

miRNA-215-5p 在 PCa 组织和细胞系中低表达。miRNA-215-5p 低表达预示着 PCa 患者预后不良。miRNA-215-5p 沉默增强了 LNCaP 细胞的活力、迁移和侵袭能力,而 DU-145 细胞中的过表达则呈现相反的趋势。PGK1 被预测为 miRNA-215-5p 的靶基因。PGK1 在 PCa 组织和细胞系中上调,其高水平预示着 PCa 的预后不良。此外,PGK1 水平与 PCa 组织中 miRNA-215-5p 水平呈负相关。PGK1 能够逆转 miRNA-215-5p 对 PCa 细胞转移潜能的调节作用。

结论

PCa 中下调的 miRNA-215-5p 与受影响患者的远处转移和不良预后密切相关。miRNA-215-5p 通过靶向和下调 PGK1 减轻 PCa 的恶性进展。

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