Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Dokl Biochem Biophys. 2021 May;496(1):32-35. doi: 10.1134/S1607672921010087. Epub 2021 Mar 10.
POU2F1 (Oct-1) is a transcription factor, the overexpression of which is found in many human malignant tumors; a significant increase in its level in cells determines the malignant potential of the tumor. POU2F1 is represented in cells by several isoforms that are transcribed from alternative promoters. In Burkitt's B-cell lymphoma Namalwa, the concentration of tissue-specific isoform Oct-1L is several times higher than in normal B cells. We tested the potential to inhibit the transcription of individual Oct-1 isoforms using the GSK3 kinase inhibitor CHIR, an aminopyrimidine derivative. We have shown that CHIR specifically affects the expression of the tissue-specific isoform Oct-1L, significantly reducing the level of mRNA and Oct-1L protein. However, CHIR does not change the amount of mRNA and protein of the ubiquitous isoform Oct-1A in Namalwa tumor cells. The results obtained show that it is possible to develop a system for selective inhibition of Oct-1 transcription factor isoforms in human cells to suppress drug resistance of tumor cells with a high POU2F1 content.
POU2F1(Oct-1)是一种转录因子,其在许多人类恶性肿瘤中过度表达;细胞中其水平的显著增加决定了肿瘤的恶性潜能。POU2F1 在细胞中由几个从不同启动子转录的同工型表示。在 Burkitt 氏 B 细胞淋巴瘤 Namalwa 中,组织特异性同工型 Oct-1L 的浓度比正常 B 细胞高几倍。我们使用 GSK3 激酶抑制剂 CHIR(一种氨基嘧啶衍生物)测试了抑制个别 Oct-1 同工型转录的潜力。我们已经表明,CHIR 特异性地影响组织特异性同工型 Oct-1L 的表达,显著降低了 mRNA 和 Oct-1L 蛋白的水平。然而,CHIR 不会改变 Namalwa 肿瘤细胞中普遍存在的同工型 Oct-1A 的 mRNA 和蛋白质含量。所得结果表明,有可能开发一种选择性抑制人类细胞中 Oct-1 转录因子同工型的系统,以抑制高 POU2F1 含量的肿瘤细胞的耐药性。