Klimek-Tomczak K, Mikula M, Dzwonek A, Paziewska A, Karczmarski J, Hennig E, Bujnicki J M, Bragoszewski P, Denisenko O, Bomsztyk K, Ostrowski J
Department of Gastroenterology, Medical Center for Postgraduate Education and Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, ul. Roentgena 5, Warsaw 02-781, Poland.
Br J Cancer. 2006 Feb 27;94(4):586-92. doi: 10.1038/sj.bjc.6602938.
The heterogeneous nuclear ribonucleoprotein K (hnRNP K) protein is an RNA-binding protein involved in many processes that compose gene expression. K protein is upregulated in the malignant processes and has been shown to modulate the expression of genes involved in mitogenic responses and tumorigenesis. To explore the possibility that there are alternative isoforms of K protein expressed in colon cancer, we amplified and sequenced K protein mRNA that was isolated from colorectal cancers as well as from normal tissues surrounding the tumours. Sequencing revealed a single G-to-A base substitution at position 274 that was found in tumours and surrounding mucosa, but not in individuals that had no colorectal tumour. This substitution most likely reflects an RNA editing event because it was not found in the corresponding genomic DNAs. Sequencing of RNA from normal colonic mucosa of patients with prior resection of colorectal cancer revealed only the wild-type K protein transcript, indicating that G274A isoform is tumour related. To our knowledge, this is the first example of an RNA editing event in cancer and its surrounding tissue, a finding that may offer a new diagnostic and treatment marker.
不均一核核糖核蛋白K（hnRNP K）是一种RNA结合蛋白，参与构成基因表达的许多过程。K蛋白在恶性过程中上调，并且已显示出可调节参与有丝分裂反应和肿瘤发生的基因的表达。为了探索在结肠癌中存在K蛋白的替代异构体的可能性，我们对从结直肠癌以及肿瘤周围正常组织中分离出的K蛋白mRNA进行了扩增和测序。测序显示在肿瘤和周围黏膜中发现了位于274位的单个G到A碱基替换，但在没有结直肠肿瘤的个体中未发现。这种替换很可能反映了一种RNA编辑事件，因为在相应的基因组DNA中未发现。对先前切除结直肠癌患者的正常结肠黏膜RNA进行测序，仅发现野生型K蛋白转录本，表明G274A异构体与肿瘤相关。据我们所知，这是癌症及其周围组织中RNA编辑事件的首个实例，这一发现可能提供一种新的诊断和治疗标志物。
