Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
Int J Mol Sci. 2024 May 19;25(10):5538. doi: 10.3390/ijms25105538.
Chromosomal instability is a hallmark of colorectal carcinogenesis and produces an accumulation of different forms of aneuploidies or broad copy number aberrations. Colorectal cancer is characterized by gain-type broad copy number aberrations, specifically in Chr20, Chr8q, Chr13 and Chr7, but their roles and mechanisms in cancer progression are not fully understood. It has been suggested that broad copy number gains might contribute to tumor development through the so-called caricature transcriptomic effect. We intend to investigate the impact of broad copy number gains on long non-coding RNAs' expression in colorectal cancer, given their well-known role in oncogenesis. The influence of such chromosomal aberrations on lncRNAs' transcriptome profile was investigated by SNP and transcriptome arrays in our series of colorectal cancer samples and cell lines. The correlation between aneuploidies and transcriptomic profiles led us to obtain a class of Over-UpT lncRNAs, which are transcripts upregulated in CRC and further overexpressed in colon tumors bearing specific chromosomal aberrations. The identified lncRNAs can contribute to a wide interaction network to establish the cancer driving effect of gain-type aneuploidies.
染色体不稳定性是结直肠癌发生的一个标志，会产生不同形式的非整倍体或广泛的拷贝数异常。结直肠癌的特征是获得型广泛的拷贝数异常，特别是在 Chr20、Chr8q、Chr13 和 Chr7 上，但它们在癌症进展中的作用和机制尚未完全阐明。有人认为，广泛的拷贝数增益可能通过所谓的漫画转录组效应促进肿瘤的发展。我们打算研究广泛的拷贝数增益对结直肠癌中长链非编码 RNA 表达的影响，因为它们在肿瘤发生中具有重要作用。在我们的一系列结直肠癌样本和细胞系中，通过 SNP 和转录组阵列研究了这些染色体异常对 lncRNAs 转录组谱的影响。非整倍体和转录组谱之间的相关性使我们获得了一类过表达的 lncRNAs，这些 lncRNAs 在 CRC 中上调，并且在携带特定染色体异常的结肠肿瘤中进一步过表达。鉴定出的 lncRNAs 可以有助于建立广泛的相互作用网络，以确定获得型非整倍体的致癌作用。
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