Aversa Rosanna, Sorrentino Anna, Esposito Roberta, Ambrosio Maria Rosaria, Amato Angela, Zambelli Alberto, Ciccodicola Alfredo, D'Apice Luciana, Costa Valerio
Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", Consiglio Nazionale delle Ricerche, Via P. Castellino 111, 80131 Naples, Italy.
Lab of Experimental Oncology and Pharmacogenomics, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione "Salvatore Maugeri", 27100 Pavia, Italy.
Int J Mol Sci. 2016 Jan 16;17(1):121. doi: 10.3390/ijms17010121.
Breast cancer is the most common tumor and the second leading cause of cancer death among woman, mainly caused by the metastatic spread. Tumor invasiveness is due to an altered expression of adhesion molecules. Among them, semaphorins are of peculiar interest. Cancer cells can manipulate alternative splicing patterns to modulate the expression of adhesion- and motility-related molecules, also at the isoform level. In this study, combining RNA-Sequencing on MCF-7 to targeted experimental validations-in human breast cell lines and breast tumor biopsies-we identified 12 new alternative splicing transcripts in genes encoding adhesion- and motility-related molecules, including semaphorins, their receptors and co-receptors. Among them, a new SEMA3F transcript is expressed in all breast cell lines and breast cancer biopsies, and is translated into a new semaphorin 3F isoform. In silico analysis predicted that most of the new putative proteins lack functional domains, potentially missing some functions and acquiring new ones. Our findings better describe the extent of alternative splicing in breast cancer and highlight the need to further investigate adhesion- and motility-related molecules to gain insights into breast cancer progression.
乳腺癌是女性中最常见的肿瘤，也是癌症死亡的第二大主要原因，主要由转移扩散引起。肿瘤侵袭性归因于黏附分子表达的改变。其中，信号素特别引人关注。癌细胞可以操纵可变剪接模式来调节黏附及运动相关分子的表达，甚至在同种型水平也是如此。在本研究中，我们将MCF-7细胞系的RNA测序与人类乳腺癌细胞系和乳腺癌活检组织的靶向实验验证相结合，在编码黏附及运动相关分子（包括信号素、其受体和共受体）的基因中鉴定出12个新的可变剪接转录本。其中，一种新的SEMA3F转录本在所有乳腺癌细胞系和乳腺癌活检组织中均有表达，并被翻译成一种新的信号素3F同种型。计算机分析预测，大多数新的假定蛋白缺乏功能域，可能缺失一些功能并获得新功能。我们的研究结果更好地描述了乳腺癌中可变剪接的程度，并强调需要进一步研究黏附及运动相关分子，以深入了解乳腺癌的进展。
