Ospedale Pediatrico Bambino Gesù, Piazza S Onofrio 4, 00165 Rome, Italy.
Int J Cancer. 2010 Jul 1;127(1):127-37. doi: 10.1002/ijc.25022.
Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors.
膀胱癌相关蛋白（BLCAP）在物种间高度保守，最初被认为是从人类膀胱癌中鉴定出来的新型候选肿瘤抑制基因。然而，关于该蛋白的调节或功能知之甚少。在这里，我们表明人类 BLCAP 转录本经历了多次 A 到 I 的编辑事件。一些新的编辑事件改变了高度保守的蛋白氨基末端，通过改变遗传编码的氨基酸，产生了不同的蛋白同工型。我们发现 ADAR1 和 ADAR2 编辑酶共同作用来编辑这个转录本，并且不同的组织显示出不同比例的编辑和未编辑的 BLCAP 转录本。此外，与相关正常组织相比，我们在星形细胞瘤、膀胱癌和结直肠癌中观察到 BLCAP 编辑水平普遍降低。在癌症中发现的新鉴定的编辑事件可能是未来研究的有用工具，可作为区分不同肿瘤中的恶性肿瘤或表观遗传变化的诊断工具。
