TRIM28 Is a Novel Regulator of CD133 Expression Associated with Cancer Stem Cell Phenotype
Kim Y.S. Potashnikova D.M. Gisina A.M. Kholodenko I.V. Kopylov A.T. Tikhonova O.V. Kurbatov L.K. Saidova A.A. Tvorogova A.V. Kholodenko R.V. Belousov P.V. Vorobjev I.A. Zgoda V.G. Yarygin K.N. Lupatov A.Y.
September 2022MDPI
International Journal of Molecular Sciences
2022#23Issue 17
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 TRIM28 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.
cancer stem cells , CD133 , cell signaling , stemness markers , TRIM28
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Laboratory of Cell Biology, V.N. Orekhovich Institute of Biomedical Chemistry, Moscow, 119121, Russian Federation
Cell Biology and Histology Department, School of Biology, M.V. Lomonosov Moscow State University, Moscow, 119234, Russian Federation
Laboratory of Systems Biology, V.N. Orekhovich Institute of Biomedical Chemistry, Moscow, 119121, Russian Federation
Transcriptome Analysis Group, Analytical Branch Department, V.N. Orekhovich Institute of Biomedical Chemistry, Moscow, 119121, Russian Federation
Department of Transcription Factors, V.A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russian Federation
Laboratory of Cell Motility, A.N. Belozersky Research Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Moscow, 119992, Russian Federation
Laboratory of Molecular Immunology, M.M. Shemyakin–Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, 117997, Russian Federation
Endocrinology Research Centre, Moscow, 117292, Russian Federation
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, V.A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russian Federation
Department of Biology, School of Sciences and Humanities, Nazarbayev University, Nur-Sultan, 010000, Kazakhstan
Laboratory of Biophotonics and Imaging, National Laboratory Astana, Nazarbayev University, Nur-Sultan, 010000, Kazakhstan
Laboratory of Cell Biology
Cell Biology and Histology Department
Laboratory of Systems Biology
Transcriptome Analysis Group
Department of Transcription Factors
Laboratory of Cell Motility
Laboratory of Molecular Immunology
Endocrinology Research Centre
Center for Precision Genome Editing and Genetic Technologies for Biomedicine
Department of Biology
Laboratory of Biophotonics and Imaging
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