miR-133a-5p 通过调节 MON2 抑制肾透明细胞癌的转移能力。
MicroRNA-133a-5p inhibiting metastatic capacity of renal clear cell carcinoma through regulating MON2.
机构信息
Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Jun;24(11):5988-5995. doi: 10.26355/eurrev_202006_21492.
OBJECTIVE
We aimed at analyzing the correlation between microRNA-133a-5p expression and clinical pathological parameters in patients with clear cell renal cell carcinoma (ccRCC) and exploring the mechanism by which microRNA-133a-5p affects the biological behavior of ccRCC cells.
PATIENTS AND METHODS
MicroRNA-133a-5p expression in ccRCC tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR), and the relationship between ATG14 expression and clinicopathological parameters of ccRCC patients was analyzed. A control group (NC mimic) and a microRNA-133a-5p overexpression group (microRNA-133a-5p mimic) were set in the ccRCC cell lines ACHN and 786-O, respectively. The impacts of microRNA-133a-5p on the proliferation and invasion of ccRCC cells were evaluated through performing Cell Counting Kit-8 (CCK-8) and transwell tests, respectively. We further explored the interaction between microRNA-133a-5p and its downstream target gene WNK2 by bioinformatics analysis and Luciferase assay.
RESULTS
Both in ccRCC tissues and cell lines, microRNA-133a-5p showed a significantly reduced expression, which could be used to predict poor prognosis of ccRCC patients. Upregulation of microRNA-133a-5p markedly blunted the proliferation and migratory capacities of HCC cells. Bioinformatics analysis suggested that microRNA-133a-5p can target MON2. In addition, qPCR assay indicated an increased expression of MON2 in ccRCC cell lines and tissues, which was negatively correlated with microRNA-133a-5p. Finally, in vitro cell reverse experiments suggested that overexpression of MON2 counteracted the inhibitory effects of overexpression of microRNA-133a-5p on the proliferation and metastatic capacity of ccRCC.
CONCLUSIONS
This study suggests that the reduced expression of microRNA-133a-5p in ccRCC tissue specimens can predict poor prognosis of ccRCC patients. At the same time, microRNA-133a-5p may suppress the proliferation capacity and metastasis of ccRCC cells by acting on MON2.
目的
分析微小 RNA-133a-5p 在透明细胞肾细胞癌（ccRCC）患者中的表达与临床病理参数的相关性，并探讨微小 RNA-133a-5p 影响 ccRCC 细胞生物学行为的机制。
方法
采用实时定量聚合酶链反应（qRT-PCR）检测 ccRCC 组织和细胞系中微小 RNA-133a-5p 的表达，并分析 ATG14 表达与 ccRCC 患者临床病理参数的关系。在 ccRCC 细胞系 ACHN 和 786-O 中分别设置对照组（NC 模拟物）和微小 RNA-133a-5p 过表达组（微小 RNA-133a-5p 模拟物）。通过细胞计数试剂盒-8（CCK-8）和 Transwell 试验分别评估微小 RNA-133a-5p 对 ccRCC 细胞增殖和侵袭的影响。我们还通过生物信息学分析和荧光素酶测定进一步探讨了微小 RNA-133a-5p 与其下游靶基因 WNK2 之间的相互作用。
结果
微小 RNA-133a-5p 在 ccRCC 组织和细胞系中表达均显著降低，可用于预测 ccRCC 患者的不良预后。微小 RNA-133a-5p 的上调显著减弱了 HCC 细胞的增殖和迁移能力。生物信息学分析表明，微小 RNA-133a-5p 可以靶向 MON2。此外，qPCR 检测表明 ccRCC 细胞系和组织中 MON2 的表达增加，与微小 RNA-133a-5p 呈负相关。最后，体外细胞逆转实验表明，MON2 的过表达抵消了微小 RNA-133a-5p 过表达对 ccRCC 增殖和转移能力的抑制作用。
结论
本研究表明，ccRCC 组织标本中微小 RNA-133a-5p 的表达降低可预测 ccRCC 患者的不良预后。同时，微小 RNA-133a-5p 可能通过作用于 MON2 抑制 ccRCC 细胞的增殖能力和转移。
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