Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
Gene. 2020 Aug 5;750:144723. doi: 10.1016/j.gene.2020.144723. Epub 2020 May 5.
The BCL2L12, one of the latest discovered members of the BCL2 family, has both pro- and anti-apoptotic roles that are cell-type-dependent. Its role in tumorigenesis is highly implicated. Sixty-three splice variants of this gene have been identified so far, with significant differences in expression patterns between various cancer cell lines. Presently, little is known regarding the regulation of expression of the BCL2L12 gene. For the vast majority of BCL2L12 gene splice variants, the 5'- and 3'-untranslated regions as well as their transcriptional regulation have not been determined yet. The aim of this study was to get insight into the regulation of the BCL2L12 gene transcription in human chronic myelogenous leukemia (K562) cell line. Our results point to the activity of novel transcription start site of the BCL2L12 gene and indicate that Sp1 and GATA-1 transcription factors could be involved in the regulation of BCL2L12 gene expression in K562 cells. The previously reported active promoter of BCL2L12 gene differs from the one we described in our study. If this novel BCL2L12 promoter is confirmed to be active in other malignancies, transcripts generated from this region could be considered as new cancer-specific biomarkers. The results of our study contribute to the better understanding of the transcriptional regulation of the BCL2L12 gene.
BCL2L12 是 BCL2 家族中最新发现的成员之一，具有促凋亡和抗凋亡作用，但其作用具有细胞依赖性。其在肿瘤发生中的作用已得到广泛证实。迄今为止，已经鉴定出该基因的 63 种剪接变体，不同癌细胞系之间的表达模式存在显著差异。目前，对于 BCL2L12 基因表达的调控知之甚少。对于绝大多数 BCL2L12 基因剪接变体，其 5'和 3'非翻译区及其转录调控尚未确定。本研究旨在深入了解人慢性髓系白血病（K562）细胞系中 BCL2L12 基因转录的调控。我们的研究结果表明 BCL2L12 基因的新型转录起始位点的活性，并表明 Sp1 和 GATA-1 转录因子可能参与 K562 细胞中 BCL2L12 基因表达的调控。之前报道的 BCL2L12 基因活性启动子与我们在本研究中描述的启动子不同。如果这个新的 BCL2L12 启动子被证实在其他恶性肿瘤中是活跃的，那么从这个区域产生的转录本可以被认为是新的癌症特异性生物标志物。我们的研究结果有助于更好地理解 BCL2L12 基因的转录调控。
