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miR-27a-3p 与 CDH5 表达呈负相关,可作为透明细胞肾细胞癌增殖和转移的诊断生物标志物。

Inverse correlation of miR-27a-3p and CDH5 expression serves as a diagnostic biomarker of proliferation and metastasis of clear cell renal carcinoma.

机构信息

Life Science Institute, Guangxi Medical University, China.

Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, China.

出版信息

Pathol Res Pract. 2021 Apr;220:153393. doi: 10.1016/j.prp.2021.153393. Epub 2021 Mar 11.

Abstract

BACKGROUND

Cadherin-5 (CDH5) is aberrantly expressed in a variety of human cancers and plays an important role in angiogenesis. The present study provides further insight into the role of miR-27a-3p in the regulation of CDH5 expression in renal clear cell carcinoma (ccRCC).

METHODS

Thedysregulation of CDH5 expression in ccRCC and its association with clinicopathological characteristics were analyzed using the TCGA database. A meta-analysis was performed to verify the alteration of CDH5 expression in ccRCC using the GEO database. Quantitative RT-PCR and immunohistochemical staining were applied to assess the transcriptional and protein levels of CDH5. TargetScan and Tarbase were employed to predict the miRNAs with the potential to target mRNA of CDH5.

RESULTS

The mRNA level of CDH5 in ccRCCwas significantly higher than in normal tissue. CDH5 mRNA expression could therefore serve as a potential diagnostic biomarker for ccRCC (AUC = 0.844). However, the reduced CDH5 transcription levels were significantly correlated with patients in the T3-4 stage, lymph node, and distant metastasis, as well as with a worse clinical outcome. We further observed that CDH5, at the protein level, was almost absent in ccRCC samples. In addition, a few databases screen showed that mir-27a-3p is a highly conserved miRNA targeting CDH5. The expression of mir-27a-3p was significantly elevated in ccRCC tissues in contrast to normal tissues. Importantly, it was positively associated with the T3-4 stage and M stage, respectively, suggesting that the expression level of mir-27a-3p could serve as a diagnostic biomarker for ccRCC (AUC = 0.775).

CONCLUSION

Our data suggest that thereduced translational level of CDH5 in ccRCC was related to the overexpression of mir-27a-3p. The higher mir-27a-3p and lower CDH5 expression significantly correlated with advanced clinical stages for ccRCC patients.

摘要

背景

钙黏蛋白 5(CDH5)在多种人类癌症中异常表达,在血管生成中发挥重要作用。本研究进一步探讨了 miR-27a-3p 在调节肾透明细胞癌(ccRCC)中 CDH5 表达中的作用。

方法

利用 TCGA 数据库分析 ccRCC 中 CDH5 表达失调及其与临床病理特征的关系。利用 GEO 数据库进行荟萃分析验证 ccRCC 中 CDH5 表达的改变。采用定量 RT-PCR 和免疫组织化学染色检测 CDH5 的转录和蛋白水平。利用 TargetScan 和 Tarbase 预测具有靶向 CDH5 mRNA 潜力的 miRNA。

结果

ccRCC 中 CDH5 的 mRNA 水平明显高于正常组织。因此,CDH5 mRNA 表达可作为 ccRCC 的潜在诊断生物标志物(AUC = 0.844)。然而,CDH5 转录水平的降低与 T3-4 期、淋巴结和远处转移以及较差的临床结局显著相关。我们进一步观察到,在 ccRCC 样本中,CDH5 蛋白水平几乎不存在。此外,一些数据库筛选表明,miR-27a-3p 是一种针对 CDH5 的高度保守 miRNA。miR-27a-3p 在 ccRCC 组织中的表达明显高于正常组织。重要的是,它与 T3-4 期和 M 期分别呈正相关,表明 miR-27a-3p 的表达水平可作为 ccRCC 的诊断生物标志物(AUC = 0.775)。

结论

我们的数据表明,ccRCC 中 CDH5 的翻译水平降低与 miR-27a-3p 的过表达有关。miR-27a-3p 表达较高和 CDH5 表达较低与 ccRCC 患者的晚期临床分期显著相关。

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