Zhou Jianhua, Liao Joshua, Zheng Xuexiu, Shen Haihong
Nantong University, Nantong, JiangSu, P. R. China.
BMB Rep. 2012 Mar;45(3):133-40. doi: 10.5483/BMBRep.2012.45.3.133.
Cancers claim millions of lives each year. Early detection that can enable a higher chance of cure is of paramount importance to cancer patients. However, diagnostic tools for many forms of tumors have been lacking. Over the last few years, studies of chimeric RNAs as biomarkers have emerged. Numerous reports using bioinformatics and screening methodologies have described more than 30,000 expressed sequence tags (EST) or cDNA sequences as putative chimeric RNAs. While cancer cells have been well known to contain fusion genes derived from chromosomal translocations, rearrangements or deletions, recent studies suggest that trans-splicing in cells may be another source of chimeric RNA production. Unlike cis-splicing, trans-splicing takes place between two pre-mRNA molecules, which are in most cases derived from two different genes, generating a chimeric non-co-linear RNA. It is possible that trans-splicing occurs in normal cells at high frequencies but the resulting chimeric RNAs exist only at low levels. However the levels of certain RNA chimeras may be elevated in cancers, leading to the formation of fusion genes. In light of the fact that chimeric RNAs have been shown to be overrepresented in various tumors, studies of the mechanisms that produce chimeric RNAs and identification of signature RNA chimeras as biomarkers present an opportunity for the development of diagnoses for early tumor detection.
癌症每年夺走数百万人的生命。能够提高治愈几率的早期检测对癌症患者至关重要。然而，许多类型肿瘤的诊断工具一直匮乏。在过去几年中，对嵌合RNA作为生物标志物的研究不断涌现。众多使用生物信息学和筛选方法的报告已将超过30000个表达序列标签（EST）或cDNA序列描述为假定的嵌合RNA。虽然众所周知癌细胞含有源自染色体易位、重排或缺失的融合基因，但最近的研究表明细胞中的反式剪接可能是嵌合RNA产生的另一个来源。与顺式剪接不同，反式剪接发生在两个前体mRNA分子之间，在大多数情况下，这两个分子来自两个不同的基因，产生一个嵌合的非共线性RNA。反式剪接可能在正常细胞中高频发生，但产生的嵌合RNA仅以低水平存在。然而，某些RNA嵌合体的水平在癌症中可能会升高，导致融合基因的形成。鉴于嵌合RNA已被证明在各种肿瘤中过度表达，研究产生嵌合RNA的机制并鉴定标志性RNA嵌合体作为生物标志物为早期肿瘤检测诊断的发展提供了机会。
