Placenta-specific novel splice variants of Rho GDP dissociation inhibitor β are highly expressed in cancerous cells.
Placenta-specific novel splice variants of Rho GDP dissociation inhibitor β are highly expressed in cancerous cells.
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DOI：
10.1186/1756-0500-5-666
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发表时间：
2012-12-03
影响因子：
1.8
通讯作者：
Mochizuki T
中科院分区：
文献类型：
--
作者：
Hatakeyama K;Fukuda Y;Ohshima K;Terashima M;Yamaguchi K;Mochizuki T
前体mRNA转录物的选择性剪接不仅在正常的分子过程中起作用，而且与癌症的发展有关。虽然正常转录物在正常组织中普遍表达，但通过异常选择性剪接事件产生的剪接变体通常在癌细胞中表达。虽然Rho GDP解离抑制剂β（ARHGDIB）基因已被发现在正常组织中广泛表达，并参与癌症的发展，但尚未研究ARHGDIB剪接变体的存在。使用逆转录聚合酶链反应和DNA测序对ARHGDIB剪接变体的存在和外显子结构进行验证分析，成功地在结肠癌、胰腺癌、胃癌和乳腺癌细胞系中鉴定了ARHGDIB的新型剪接变体，即6a、6b和6c。实时定量聚合酶链反应分析表明，这些变异体也在正常胎盘组织中高度表达，但在其他类型的正常组织中不表达。ARHGDIB变体6a、6b和6c的表达似乎仅限于癌细胞和正常胎盘组织，表明这些变体具有癌症特异性功能，因此是潜在的癌症相关生物标志物。
Alternative splicing of pre-mRNA transcripts not only plays a role in normal molecular processes but is also associated with cancer development. While normal transcripts are ubiquitously expressed in normal tissues, splice variants created through abnormal alternative splicing events are often expressed in cancer cells. Although the Rho GDP dissociation inhibitor β (ARHGDIB) gene has been found to be ubiquitously expressed in normal tissues and involved in cancer development, the presence of splice variants of ARHGDIB has not yet been investigated. Validation analysis for the presence of and exon structures of splice variants of ARHGDIB, performed using reverse-transcriptase polymerase chain reaction and DNA sequencing, successfully identified novel splice variants of ARHGDIB, that is, 6a, 6b, and 6c, in colon, pancreas, stomach, and breast cancer cell lines. Quantitative real-time polymerase chain reaction analysis showed that these variants were also highly expressed in normal placental tissue but not in other types of normal tissue. Expression of ARHGDIB variants 6a, 6b, and 6c appears to be restricted to cancer cells and normal placental tissue, suggesting that these variants possess cancer-specific functions and, as such, are potential cancer-related biomarkers.