The expression profiles of piRNAs and their interacting Piwi proteins in cellular model of renal development: Focus on Piwil1 in mitosis

IF 4.3 3区 生物学 Q2 CELL BIOLOGY European journal of cell biology Pub Date : 2024-07-15 DOI:10.1016/j.ejcb.2024.151444
Marek Kazimierczyk, Agnieszka Fedoruk-Wyszomirska, Dorota Gurda-Woźna, Eliza Wyszko, Agata Swiatkowska, Jan Wrzesinski
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Abstract

Piwi proteins and Piwi interacting RNAs, piRNAs, presented in germline cells play a role in transposon silencing during germline development. In contrast, the role of somatic Piwi proteins and piRNAs still remains obscure. Here, we characterize the expression pattern and distribution of piRNAs in human renal cells in terms of their potential role in kidney development. Further, we show that all PIWI genes are expressed at the RNA level, however, only PIWIL1 gene is detected at the protein level by western blotting in healthy and cancerous renal cells. So far, the expression of human Piwil1 protein has only been shown in testes and cancer cells, but not in healthy somatic cell lines. Since we observe only Piwil1 protein, the regulation of other PIWI genes is probably more intricated, and depends on environmental conditions. Next, we demonstrate that downregulation of Piwil1 protein results in a decrease in the rate of cell proliferation, while no change in the level of apoptotic cells is observed. Confocal microscopy analysis reveals that Piwil1 protein is located in both cellular compartments, cytoplasm and nucleus in renal cells. Interestingly, in nucleus region Piwil1 is observed close to the spindle during all phases of mitosis in all tested cell lines. It strongly indicates that Piwil1 protein plays an essential role in proliferation of somatic cells. Moreover, involvement of Piwil1 in cell division could, at least partly, explain invasion and metastasis of many types of cancer cells with upregulation of PIWIL1 gene expression. It also makes Piwil1 protein as a potential target in the anticancer therapy.

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肾脏发育细胞模型中 piRNA 及其相互作用的 Piwi 蛋白的表达谱:聚焦有丝分裂中的 Piwil1
生殖细胞中的 Piwi 蛋白和 Piwi 交互 RNA(piRNA)在生殖细胞发育过程中的转座子沉默中发挥作用。相比之下,体细胞中的 Piwi 蛋白和 piRNAs 的作用仍不明显。在这里,我们从 piRNAs 在肾脏发育过程中的潜在作用出发,描述了它们在人类肾脏细胞中的表达模式和分布。此外,我们还发现,所有 PIWI 基因都在 RNA 水平上表达,但在健康和癌变肾细胞中,只有 PIWIL1 基因能通过 Western 印迹在蛋白质水平上被检测到。迄今为止,人类 Piwil1 蛋白的表达只在睾丸和癌细胞中出现过,而在健康的体细胞系中没有发现。由于我们只观察到 Piwil1 蛋白,其他 PIWI 基因的调控可能更为复杂,并取决于环境条件。接下来,我们证明下调 Piwil1 蛋白会导致细胞增殖率下降,而凋亡细胞的水平却没有变化。共聚焦显微镜分析显示,Piwil1 蛋白位于肾细胞的细胞质和细胞核两个细胞区。有趣的是,在所有测试的细胞系中,在有丝分裂的所有阶段,在细胞核区域都能观察到 Piwil1 靠近纺锤体。这有力地表明,Piwil1 蛋白在体细胞增殖过程中发挥着重要作用。此外,Piwil1 参与细胞分裂至少可以部分解释为什么许多类型的癌细胞会随着 PIWIL1 基因表达的上调而发生侵袭和转移。这也使 Piwil1 蛋白成为抗癌治疗的潜在靶点。
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来源期刊
European journal of cell biology
European journal of cell biology 生物-细胞生物学
CiteScore
7.30
自引率
1.50%
发文量
80
审稿时长
38 days
期刊介绍: The European Journal of Cell Biology, a journal of experimental cell investigation, publishes reviews, original articles and short communications on the structure, function and macromolecular organization of cells and cell components. Contributions focusing on cellular dynamics, motility and differentiation, particularly if related to cellular biochemistry, molecular biology, immunology, neurobiology, and developmental biology are encouraged. Manuscripts describing significant technical advances are also welcome. In addition, papers dealing with biomedical issues of general interest to cell biologists will be published. Contributions addressing cell biological problems in prokaryotes and plants are also welcome.
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