Laboratory of Cell Biology, V.N. Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, Russia.
Cell Biology and Histology Department, School of Biology, M.V. Lomonosov Moscow State University, 119234 Moscow, Russia.
Int J Mol Sci. 2022 Aug 30;23(17):9874. doi: 10.3390/ijms23179874.
CD133 is an extensively studied marker of the most malignant tumor cell population, designated as cancer stem cells (CSCs). However, the function of this glycoprotein and its involvement in cell regulatory cascades are still poorly understood. Here we show a positive correlation between the level of CD133 plasma membrane expression and the proliferative activity of cells of the Caco-2, HT-29, and HUH7 cancer cell lines. Despite a substantial difference in the proliferative activities of cell populations with different levels of CD133 expression, transcriptomic and proteomic profiling revealed only minor distinctions between them. Nonetheless, a further in silico assessment of the differentially expressed transcripts and proteins revealed 16 proteins that could be involved in the regulation of CD133 expression; these were assigned ranks reflecting the apparent extent of their involvement. Among them, the TRIM28 transcription factor had the highest rank. The prominent role of TRIM28 in CD133 expression modulation was confirmed experimentally in the Caco2 cell line clones: the knockout, though not the knockdown, of the gene downregulated CD133. These results for the first time highlight an important role of the TRIM28 transcription factor in the regulation of CD133-associated cancer cell heterogeneity.
CD133 是一种广泛研究的最恶性肿瘤细胞群体标志物，被指定为癌症干细胞 (CSCs)。然而，这种糖蛋白的功能及其在细胞调节级联中的作用仍知之甚少。在这里，我们显示 CD133 质膜表达水平与 Caco-2、HT-29 和 HUH7 癌细胞系的细胞增殖活性之间存在正相关。尽管具有不同 CD133 表达水平的细胞群体的增殖活性存在很大差异，但转录组和蛋白质组分析仅显示它们之间存在微小差异。尽管如此，对差异表达的转录本和蛋白质的进一步计算机评估揭示了 16 种可能参与 CD133 表达调节的蛋白质；这些蛋白质被赋予反映其明显参与程度的等级。其中，TRIM28 转录因子的等级最高。在 Caco2 细胞系克隆中，实验证实了 TRIM28 在 CD133 表达调控中的突出作用：尽管基因 不是敲低，而是敲除，也下调了 CD133。这些结果首次强调了 TRIM28 转录因子在调节与 CD133 相关的癌细胞异质性中的重要作用。
