BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells
BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells
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BCLAF1及其剪接调节因子SRSF10调节结肠癌细胞的致瘤潜力
DOI：
10.1038/ncomms5581
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发表时间：
2014-08-01
影响因子：
16.6
通讯作者：
Feng, Ying
中科院分区：
文献类型：
--
作者：
Zhou, Xuexia;Li, Xuebing;Feng, Ying
Bcl-2相关转录因子1（BCLAF 1）参与多种生物学过程。虽然已经鉴定了BCLAF 1的几种剪接变体，但关于BCLAF 1剪接如何调节或选择性剪接对其发育功能的贡献知之甚少。在这里，我们发现，包括替代外显子5a显着增加，在结直肠癌（CRC）样本。敲低BCLAF 1蛋白亚型导致外显子5a包含抑制生长，其过度表达增加致瘤潜力。我们还发现，剪接因子SRSF 10刺激包含外显子5a，并具有生长诱导活性。重要的是，在临床CRC样本中观察到SRSF 10表达的上调与BCLAF 1 exon 5a的增加相平行，两者都与较高的肿瘤分级相关。这些发现确定SRSF 10是BCLAF 1前mRNA剪接和维持人类结肠癌细胞致癌特征的关键调节因子。
Bcl-2-associated transcription factor 1 (BCLAF1) is known to be involved in multiple biological processes. Although several splice variants of BCLAF1 have been identified, little is known about how BCLAF1 splicing is regulated or the contribution of alternative splicing to its developmental functions. Here we find that inclusion of alternative exon5a was significantly increased in colorectal cancer (CRC) samples. Knockdown of the BCLAF1 protein isoform resulting from exon5a inclusion inhibited growth and that its overexpression increased tumorigenic potential. We also found that the splicing factor SRSF10 stimulates inclusion of exon5a and has growth-inducing activity. Importantly, the upregulation of SRSF10 expression observed in clinical CRC samples parallels the increased inclusion ofBCLAF1exon5a, both of which are associated with higher tumour grade. These findings identify SRSF10 as a key regulator of BCLAF1 pre-mRNA splicing and the maintenance of oncogenic features in human colon cancer cells.