Hatakeyama Keiichi, Fukuda Yorikane, Ohshima Keiichi, Terashima Masanori, Yamaguchi Ken, Mochizuki Tohru
Medical Genetics Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
BMC Res Notes. 2012 Dec 3;5:666. doi: 10.1186/1756-0500-5-666.
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.
前体mRNA转录本的可变剪接不仅在正常分子过程中发挥作用，还与癌症发展相关。正常转录本在正常组织中普遍表达，而通过异常可变剪接事件产生的剪接变体通常在癌细胞中表达。尽管已发现Rho GDP解离抑制剂β（ARHGDIB）基因在正常组织中普遍表达并参与癌症发展，但尚未对ARHGDIB剪接变体的存在进行研究。
使用逆转录聚合酶链反应和DNA测序对ARHGDIB剪接变体的存在及其外显子结构进行验证分析，成功在结肠、胰腺、胃和乳腺癌细胞系中鉴定出ARHGDIB的新型剪接变体，即6a、6b和6c。定量实时聚合酶链反应分析表明，这些变体在正常胎盘组织中也高度表达，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，这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。
