Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Int J Mol Sci. 2023 Aug 19;24(16):12986. doi: 10.3390/ijms241612986.
Clear cell renal cell carcinoma (ccRCC) accounts for 80-90% of kidney cancers worldwide. Small C-terminal domain phosphatases CTDSP1, CTDSP2, and CTDSPL (also known as SCP1, 2, 3) are involved in the regulation of several important pathways associated with carcinogenesis. In various cancer types, these phosphatases may demonstrate either antitumor or oncogenic activity. Tumor-suppressive activity of these phosphatases in kidney cancer has been shown previously, but in general case, the antitumor activity may be dependent on the choice of cell line. In the present work, transfection of the Caki-1 cell line (ccRCC morphologic phenotype) with expression constructs containing the coding regions of these genes resulted in inhibition of cell growth in vitro in the case of ( < 0.001) and ( < 0.05) but not . The analysis of The Cancer Genome Atlas (TCGA) data showed differential expression of some of genes and of their target, . These results were confirmed by quantitative RT-PCR using an independent sample of primary ccRCC tumors ( = 52). We observed downregulation and found a positive correlation of expression for two gene pairs: and ( = 0.76; < 0.001) and and ( = 0.38; < 0.05). Survival analysis based on TCGA data demonstrated a strong association of lower expression of , , , and with poor survival of ccRCC patients ( < 0.001). In addition, according to TCGA, , , and were differently expressed in two subtypes of ccRCC-ccA and ccB, characterized by different survival rates. These results confirm that and have tumor suppressor properties in ccRCC and reflect their association with the more aggressive ccRCC phenotype.
透明细胞肾细胞癌 (ccRCC) 占全球肾癌的 80-90%。小 C 端结构域磷酸酶 CTDSP1、CTDSP2 和 CTDSPL（也称为 SCP1、2、3）参与调节与致癌作用相关的几种重要途径。在各种癌症类型中，这些磷酸酶可能表现出抗肿瘤或致癌活性。这些磷酸酶在肾癌中的肿瘤抑制活性以前已经得到证实，但一般情况下，抗肿瘤活性可能取决于细胞系的选择。在本工作中，用包含这些基因编码区的表达构建体转染 Caki-1 细胞系（ccRCC 形态表型），导致体外细胞生长受到抑制（<0.001）和（<0.05），但不是（<0.05）。对癌症基因组图谱 (TCGA) 数据的分析显示，一些基因及其靶基因的表达存在差异。使用独立的原发性 ccRCC 肿瘤样本（=52）进行定量 RT-PCR 验证了这些结果。我们观察到下调，并发现两个基因对的表达呈正相关：和（=0.76；<0.001）和和（=0.38；<0.05）。基于 TCGA 数据的生存分析表明，下调、、和与 ccRCC 患者的不良生存密切相关（<0.001）。此外，根据 TCGA，在 ccA 和 ccB 两种 ccRCC 亚型中，和、和的表达不同，这两种亚型的生存率也不同。这些结果证实和在 ccRCC 中具有肿瘤抑制特性，并反映了它们与更具侵袭性的 ccRCC 表型的关联。
