Poursani Ensieh M, Mehravar Majid, Soltani Bahram Mohammad, Mowla Seyed Javad
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Tumour Biol. 2017 Oct;39(10):1010428317724280. doi: 10.1177/1010428317724280.
OCT4 is a crucial transcription factor that maintains self-renewal and pluripotency of embryonic stem and embryonic carcinoma cells. The human OCT4 gene can generate at least three variants (OCT4A, OCT4B, and OCTB1) via alternative splicing and alternative promoters. It has been previously reported that OCT4A is the main isoform, retaining stemness state in embryonic stem and embryonic carcinoma cells. There are several reports on the expression of OCT4A, OCT4B, and OCT4B1 in some cancers and tumor cells. The expression of OCT4 in cancer tissues and cell lines appeared to be highly controversial since it was believed that OCT4 is exclusively expressed in embryonic stem/embryonic carcinoma cells. Here, we are reporting the detection of a novel alternatively spliced variant of OCT4, OCT4B2, in several pluripotent and tumor cell lines. Moreover, the expression pattern of OCT4B2 in the course of neural differentiation of NT2 and NCCIT, embryonic carcinoma cells, was similar to that of OCT4A. OCT4B2 was highly expressed in undifferentiated cells; however, its expression was sharply downregulated upon induction of differentiation. Overexpression of OCT4B2 did not affect the distribution of cells in different cell-cycle phases of transfected cells, compared to the mock transfected cells. Interestingly, the expression of OCT4B2 transcript was elevated under the heat-shock induction. In conclusion, we are reporting a new variant of OCT4, which is expressed under different physiological conditions. The finding shed more light on complexity of OCT4 expression and functions.
OCT4是一种关键的转录因子,可维持胚胎干细胞和胚胎癌细胞的自我更新及多能性。人类OCT4基因可通过可变剪接和可变启动子产生至少三种变体(OCT4A、OCT4B和OCTB1)。此前有报道称,OCT4A是主要的异构体,在胚胎干细胞和胚胎癌细胞中保持干性状态。关于OCT4A、OCT4B和OCT4B1在某些癌症和肿瘤细胞中的表达已有多篇报道。OCT4在癌组织和细胞系中的表达似乎极具争议,因为人们认为OCT4仅在胚胎干细胞/胚胎癌细胞中表达。在此,我们报告在多种多能和肿瘤细胞系中检测到一种新的OCT4可变剪接变体OCT4B2。此外,OCT4B2在胚胎癌细胞NT2和NCCIT神经分化过程中的表达模式与OCT4A相似。OCT4B2在未分化细胞中高表达;然而,在诱导分化后其表达急剧下调。与空载体转染细胞相比,OCT4B2的过表达不影响转染细胞在不同细胞周期阶段的分布。有趣的是,在热休克诱导下OCT4B2转录本的表达升高。总之,我们报告了一种新的OCT4变体,其在不同生理条件下表达。这一发现为OCT4表达和功能的复杂性提供了更多线索。