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Identification of new SOX2OT transcript variants highly expressed in human cancer cell lines and down regulated in stem cell differentiation

机译:鉴定在人类癌细胞系中高表达并在干细胞分化中下调的新SOX2OT转录物变体

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Long non-coding RNAs are manifested as a new paradigm of molecular effectors in a wide range of human diseases. Human SOX2 overlapping transcript (SOX2OT) gene can generate six lncRNA transcript variants which are functionally assumed to be correlated with cellular differentiation and carcinogenesis. However, the circumstances determining expressional and functional differences between SOX2OT transcript variants remain to be explored. Here, we studied the expression of all SOX2OT transcript variants specifically in five human cancer cell lines by real-time RT-PCR. Changes of the new SOX2OT transcript variants expression were measured during the NT2 teratocarcinoma cell line neuronal-like differentiation and were compared to pluripotency regulators, SOX2 and OCT4A gene expressions. Surprisingly, we identified two new SOX2OT transcripts, named SOX2OT-7, SOX2OT-8 which lack exon 8. We discovered that beside active proximal and distal SOX2OT promoters, different cancer cell lines express high levels of some SOX2OT transcript variants differentially by alternative splicing. Significantly, both SOX2OT-7 and SOX2OT-8 are highly expressed in human cancer cell lines coinciding with SOX2, one of the pluripotency regulators. Our results revealed that SOX2OT-7 is almost the most abundant form of SOX2OT transcript variants in the examined cancer cell lines particularly in NT2 teratocarcinoma cell line where its expression falls upon neuronal-like differentiation similar to SOX2 and OCT4A. We suggest that at least some of SOX2OT transcripts are significantly associated with cancer and stem cell related pathways.
机译:长的非编码RNA被证明是人类疾病中分子效应子的新范式。人SOX2重叠转录本(SOX2OT)基因可以产生六个lncRNA转录本变体,这些变体在功能上被认为与细胞分化和致癌作用相关。但是,确定SOX2OT转录变体之间表达和功能差异的情况仍有待探索。在这里,我们通过实时RT-PCR研究了所有SOX2OT转录变体在5种人类癌细胞系中的表达。在NT2畸形癌细胞系神经元样分化过程中测量了新的SOX2OT转录变体表达的变化,并将其与多能性调节剂,SOX2和OCT4A基因表达进行了比较。出乎意料的是,我们发现了两个新的SOX2OT转录本,分别名为SOX2OT-7,SOX2OT-8,它们缺少外显子8。我们发现,除了活跃的近端和远端SOX2OT启动子外,不同的癌细胞系还通过选择性剪接差异表达高水平的SOX2OT转录本变体。重要的是,SOX2OT-7和SOX2OT-8在与多能性调节剂之一SOX2一致的人类癌细胞系中高表达。我们的结果表明,在所检查的癌细胞系中,特别是在NT2畸形癌细胞系中,SOX2OT-7几乎是最丰富的SOX2OT转录变体形式,在NT2畸形癌细胞系中,其表达类似于SOX2和OCT4A,属于神经元样分化。我们建议,至少一些SOX2OT转录本与癌症和干细胞相关途径显着相关。

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