Rea Jessica, Carissimo Annamaria, Trisciuoglio Daniela, Illi Barbara, Picard Daniel, Remke Marc, Laneve Pietro, Caffarelli Elisa
Department of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, 00185 Rome, Italy.
Institute for Applied Mathematics "Mauro Picone", CNR, 80131 Naples, Italy.
Cancers (Basel). 2021 Jul 30;13(15):3853. doi: 10.3390/cancers13153853.
The impact of protein-coding genes on cancer onset and progression is a well-established paradigm in molecular oncology. Nevertheless, unveiling the contribution of the noncoding genes-including long noncoding RNAs (lncRNAs)-to tumorigenesis represents a great challenge for personalized medicine, since they (i) constitute the majority of the human genome, (ii) are essential and flexible regulators of gene expression and (iii) present all types of genomic alterations described for protein-coding genes. LncRNAs have been increasingly associated with cancer, their highly tissue- and cancer type-specific expression making them attractive candidates as both biomarkers and therapeutic targets. Medulloblastoma is one of the most common malignant pediatric brain tumors. Group 3 is the most aggressive subgroup, showing the highest rate of metastasis at diagnosis. Transcriptomics and reverse genetics approaches were combined to identify lncRNAs implicated in Group 3 Medulloblastoma biology. Here we present the first collection of lncRNAs dependent on the activity of the MYC oncogene, the major driver gene of Group 3 Medulloblastoma. We assessed the expression profile of selected lncRNAs in Group 3 primary tumors and functionally characterized these species. Overall, our data demonstrate the direct involvement of three lncRNAs in Medulloblastoma cancer cell phenotypes.
蛋白质编码基因对癌症发生和进展的影响是分子肿瘤学中一个已确立的范例。然而，揭示非编码基因（包括长链非编码RNA，lncRNAs）对肿瘤发生的贡献对个性化医疗来说是一个巨大挑战，因为它们：（i）构成了人类基因组的大部分；（ii）是基因表达的重要且灵活的调节因子；（iii）呈现出蛋白质编码基因所描述的所有类型的基因组改变。lncRNAs与癌症的关联日益增加，它们高度的组织和癌症类型特异性表达使其成为作为生物标志物和治疗靶点的有吸引力的候选者。髓母细胞瘤是最常见的儿童恶性脑肿瘤之一。3组是最具侵袭性的亚组，在诊断时转移率最高。转录组学和反向遗传学方法相结合，以鉴定与3组髓母细胞瘤生物学相关的lncRNAs。在此，我们展示了首批依赖于MYC癌基因活性的lncRNAs集合，MYC癌基因是3组髓母细胞瘤的主要驱动基因。我们评估了选定lncRNAs在3组原发性肿瘤中的表达谱，并对这些物种进行了功能表征。总体而言，我们的数据证明了三种lncRNAs直接参与髓母细胞瘤癌细胞表型。
