Laboratory for Molecular Biology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042, Belgrade, Serbia.
CNR Institute of Molecular Genetics "Luigi-Luca Cavalli-Sforza" Unit of Bologna, Via di Barbiano 1/10, 40136, Bologna, Italy.
Histochem Cell Biol. 2024 May;161(5):435-444. doi: 10.1007/s00418-024-02272-2. Epub 2024 Feb 23.
Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children and adolescents. Respecting the age of the patients and the tumor aggressiveness, investigation of the molecular mechanisms of RMS tumorigenesis is directed toward the identification of novel therapeutic targets. To contribute to a better understanding of the molecular pathology of RMS, we investigated ankyrin repeat domain 1 (ANKRD1), designated as a potential marker for differential diagnostics. In this study, we used three RMS cell lines (SJRH30, RD, and HS-729) to assess its expression profile, intracellular localization, and turnover. They express wild-type ANKRD1, as judged by the sequencing of the open reading frame. Each cell line expressed a different amount of ANKRD1 protein, although the transcript level was similar. According to western blot analysis, ANKRD1 protein was expressed at detectable levels in the SJRH30 and RD cells (SJRH30 > RD), but not in the HS-729, even after immunoprecipitation. Immunocytochemistry revealed nuclear and cytoplasmic localization of ANKRD1 in all examined cell lines. Moreover, the punctate pattern of ANKRD1 staining in the nuclei of RD and HS-729 cells overlapped with coilin, indicating its association with Cajal bodies. We have shown that RMS cells are not able to overexpress ANKRD1 protein, which can be attributed to its proteasomal degradation. The unsuccessful attempt to overexpress ANKRD1 in RMS cells indicates the possibility that its overexpression may have detrimental effects for RMS cells and opens a window for further research into its role in RMS pathogenesis and for potential therapeutic targeting.
横纹肌肉瘤 (RMS) 是儿童和青少年中最常见的软组织恶性肿瘤。为了尊重患者的年龄和肿瘤的侵袭性,对 RMS 肿瘤发生的分子机制的研究旨在确定新的治疗靶点。为了更好地理解 RMS 的分子病理学,我们研究了锚蛋白重复域 1 (ANKRD1),将其指定为用于鉴别诊断的潜在标志物。在这项研究中,我们使用了三种 RMS 细胞系 (SJRH30、RD 和 HS-729) 来评估其表达谱、细胞内定位和周转率。根据开放阅读框的测序判断,它们表达野生型 ANKRD1。每个细胞系表达的 ANKRD1 蛋白量不同,尽管转录水平相似。根据 Western blot 分析,SJRH30 和 RD 细胞中可检测到 ANKRD1 蛋白的表达 (SJRH30 > RD),但 HS-729 细胞中则没有,即使进行免疫沉淀也是如此。免疫细胞化学显示 ANKRD1 在所有检测到的细胞系中均定位于核内和细胞质。此外,RD 和 HS-729 细胞核中 ANKRD1 染色的点状模式与 coilin 重叠,表明其与 Cajal 体有关。我们已经表明,RMS 细胞不能过表达 ANKRD1 蛋白,这可以归因于其蛋白酶体降解。在 RMS 细胞中过表达 ANKRD1 的尝试失败表明,其过表达可能对 RMS 细胞有不利影响,并为进一步研究其在 RMS 发病机制中的作用和潜在的治疗靶点开辟了一扇窗口。