Engelhardt Institute of Molecular Biology of Russian Academy of Sciences, Moscow, Russia.
Dokl Biochem Biophys. 2022 Apr;503(1):76-79. doi: 10.1134/S1607672922020089. Epub 2022 May 10.
Overexpression of the transcription factor POU2F1 (Oct-1) increases the malignant potential of the tumor and determines the unfavorable prognosis for both solid and hematological cases of the disease in human carcinogenesis. The Oct-1 level determines the rate of development of the disease in acute myelodysplastic leukemia (AML), and a decrease in its expression significantly delays the development of leukemia in mice; however, a complete knockout of Oct-1 leads to the death of the animals. POU2F1 (Oct-1) is expressed as several isoforms transcribed from alternative promoters. They include both ubiquitous and tissue-specific isoforms. It was shown that in Burkitt's lymphoma Namalwa cells 5-azacytidine specifically suppresses the expression of the tissue-specific isoform Oct-1L mRNA (level of Oct-1L is abnormally increased in these cells), while not causing changes in the amount of the ubiquitous isoform Oct-1A mRNA. These results show that it is possible to selectively reduce the transcription level of the Oct-1L isoform aberrantly expressed in human tumor cells.
转录因子 POU2F1（Oct-1）的过度表达增加了肿瘤的恶性潜能，并决定了人类肿瘤发生中实体瘤和血液系统肿瘤病例的不良预后。Oct-1 水平决定了急性骨髓性白血病（AML）的疾病发展速度，其表达的降低显著延缓了白血病在小鼠中的发展；然而，Oct-1 的完全敲除导致动物死亡。POU2F1（Oct-1）表达为从不同启动子转录的几种异构体。它们包括普遍存在的和组织特异性的异构体。已经表明，在 Burkitt 淋巴瘤 Namalwa 细胞中，5-氮杂胞苷特异性抑制组织特异性异构体 Oct-1L mRNA 的表达（这些细胞中 Oct-1L 的水平异常升高），而不会导致普遍存在的异构体 Oct-1A mRNA 数量的变化。这些结果表明，可以选择性地降低人肿瘤细胞中异常表达的 Oct-1L 异构体的转录水平。
