Institute of Biochemistry and Genetics - Subdivision, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russian Federation, 450054.
Bashkir State Medical University, Ufa, Russian Federation, 450008.
Mol Biol Rep. 2021 Jul;48(7):5561-5569. doi: 10.1007/s11033-021-06573-w. Epub 2021 Jul 24.
Renal cell carcinoma is the most common form of kidney cancer in adults. DNA methylation of regulatory sequences at the genomic level and interaction between microRNAs and the messenger RNAs of target genes at the posttranscriptional level contribute to the dynamic regulation of gene activity. Aberrations in these mechanisms can result in impaired functioning of cell signaling pathways, such as that observed in malignant tumors. We hypothesized that microRNA genes methylation may be associated with renal cancer in patients.
We examined methylation levels of 22 microRNA genes in tumor and normal kidney tissue of 30 patients with TNM Stage III clear cell renal cell carcinoma using a pathway-specific real-time polymerase chain reaction array (EpiTect Methyl II PCR Arrays, Qiagen). MicroRNA expression analysis by quantitative polymerase chain reaction was also performed. Significant differences in methylation levels were found in two genes and in two clusters of microRNA genes. MicroRNA-23b/-24-1/-27b, microRNA -30c-1/-30e and let-7 g was hypermetylated in clear cell renal cell carcinoma tissue, microRNA -301a was hypomethylated in tumor compared with the adjacent normal tissues. Expression of microRNA-301a, microRNA-23b in the clear cell renal cell carcinoma tissues was significantly overexpressed when compared with the adjacent normal tissues and let-7 g was significantly downregulated in tumor.
Our results may indicate the contribution of microRNA-301a, microRNA-23b and let-7 g in the pathogenesis of renal cancer, but further studies are needed to determine the functional significance of the detected changes.
肾细胞癌是成年人中最常见的肾癌形式。在基因组水平上，调节序列的 DNA 甲基化和在转录后水平上 microRNA 与靶基因的信使 RNA 之间的相互作用，有助于基因活性的动态调节。这些机制的异常可能导致细胞信号通路功能受损，如恶性肿瘤中观察到的那样。我们假设 microRNA 基因甲基化可能与患者的肾癌有关。
我们使用特定于途径的实时聚合酶链反应阵列（EpiTect Methyl II PCR Arrays，Qiagen）检查了 30 名 III 期透明细胞肾细胞癌患者肿瘤和正常肾组织中 22 个 microRNA 基因的甲基化水平。还通过定量聚合酶链反应进行了 microRNA 表达分析。在两个基因和两个 microRNA 基因簇中发现了甲基化水平的显著差异。microRNA-23b/-24-1/-27b、microRNA-30c-1/-30e 和 let-7g 在透明细胞肾细胞癌组织中呈高甲基化，microRNA-301a 在肿瘤中与相邻正常组织相比呈低甲基化。与相邻正常组织相比，microRNA-301a 和 microRNA-23b 在透明细胞肾细胞癌组织中的表达明显过表达，而 let-7g 在肿瘤中的表达明显下调。
我们的结果可能表明 microRNA-301a、microRNA-23b 和 let-7g 在肾癌发病机制中的作用，但需要进一步研究来确定检测到的变化的功能意义。
