Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece.
Laboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", 15310 Athens, Greece.
Int J Mol Sci. 2019 Feb 21;20(4):937. doi: 10.3390/ijms20040937.
Skin cancer represents the most common human malignancy, and it includes BCC, SCC, and melanoma. Since melanoma is one of the most aggressive types of cancer, we have herein attempted to develop a gene-specific intron retention signature that can distinguish BCC and SCC from melanoma biopsy tumors.
Intron retention events were examined through RT-sqPCR protocols, using total RNA preparations derived from BCC, SCC, and melanoma Greek biopsy specimens. Intron-hosted miRNA species and their target transcripts were predicted via the miRbase and miRDB bioinformatics platforms, respectively. Ιntronic ORFs were recognized through the ORF Finder application. Generation and visualization of protein interactomes were achieved by the IntAct and Cytoscape softwares, while tertiary protein structures were produced by using the I-TASSER online server.
and genes proved to undergo intron retention specifically in melanoma. Interaction maps of proteins encoded by genes being potentially targeted by retained intron-accommodated miRNAs were generated and was additionally delivered to our melanoma-specific signature. Novel ORFs were identified in and introns, with potentially critical roles in melanoma development.
The property of , , and genes to retain specific introns could be clinically used to molecularly differentiate non-melanoma from melanoma tumors.
皮肤癌是最常见的人类恶性肿瘤，包括基底细胞癌、鳞状细胞癌和黑色素瘤。由于黑色素瘤是最具侵袭性的癌症之一，我们试图在此开发一种基因特异性内含子保留特征，以区分黑色素瘤活检肿瘤与基底细胞癌和鳞状细胞癌。
通过 RT-sqPCR 方案检查内含子保留事件，使用源自希腊基底细胞癌、鳞状细胞癌和黑色素瘤活检标本的总 RNA 制剂。通过 miRbase 和 miRDB 生物信息学平台分别预测内含子宿主 miRNA 物种及其靶转录本。通过 ORF Finder 应用程序识别内含子 ORF。通过 IntAct 和 Cytoscape 软件生成和可视化蛋白质相互作用组，而三级蛋白质结构则通过 I-TASSER 在线服务器生成。
发现 和 基因在黑色素瘤中特异性地经历内含子保留。生成了由潜在受保留内含子容纳 miRNA 靶向的基因编码的蛋白质的互作图谱，并将 添加到我们的黑色素瘤特异性特征中。在 和 内含子中鉴定了新的 ORF，它们在黑色素瘤发生中可能具有关键作用。
、 和 基因保留特定内含子的特性可用于临床区分非黑色素瘤和黑色素瘤肿瘤的分子差异。
