Gene fusions and their fusion products have been recognized as ideal biomarkers and drug targets for cancer. However, few recurrent gene fusions were found in colorectal cancer (CRC), despite comprehensive studies. We believe that chimeric RNAs, in the absence of chromosomal rearrangement, may represent a new repertoire of biomarkers and/or therapeutic targets in CRC. In this study, we aim to identify such recurrent chimeric RNAs, and investigate their clinical implications. To do so, we performed extensive data mining for chimeric RNAs using The Cancer Genome Atlas CRC RNA-Seq datasets. Multiple filtering criteria were applied, and the landscape of chimeric RNAs at multiple levels, from various angles, was analyzed. Eleven frequent, cancer biased chimeric RNAs were validated. The expression of RRM2-C2orf48 correlates with poor clinical outcomes, while the expression of parental RRM2 and C2orf48 correlates with positive clinical outcomes. Mechanistically, it is a product of cis-splicing between adjacent genes. Silencing of RRM2-C2orf48 resulted in reduced cellular proliferation in colon cancer cells, whereas overexpressed chimera promoted cell proliferation. These findings suggest that frequent chimeric RNAs are present in CRCs, and that chimeric RNAs may have different expression profiles and functions from parental genes, thus representing a new repertoire of biomarkers and therapeutic targets.

基因融合及其融合产物已被公认为理想的癌症生物标志物和药物靶点。然而，尽管进行了全面研究，但在结直肠癌 (CRC) 中发现的复发性基因融合很少。我们认为，在没有染色体重排的情况下，嵌合 RNA 可能代表 CRC 中新的生物标志物和/或治疗靶点。在这项研究中，我们的目标是识别这种反复出现的嵌合 RNA，并研究它们的临床意义。为此，我们使用癌症基因组图谱 CRC RNA-Seq 数据集对嵌合 RNA 进行了广泛的数据挖掘。应用了多种过滤标准，并从不同角度分析了多层次嵌合 RNA 的景观。验证了 11 个常见的、偏向于癌症的嵌合 RNA。RRM2-C2orf48的表达与不良临床结果相关，而父母RRM2和C2orf48的表达与阳性临床结果相关。从机制上讲，它是相邻基因之间顺式剪接的产物。RRM2-C2orf48 的沉默导致结肠癌细胞中的细胞增殖减少，而过表达的嵌合体促进细胞增殖。这些发现表明，CRC 中存在频繁的嵌合 RNA，并且嵌合 RNA 可能具有与亲本基因不同的表达谱和功能，因此代表了新的生物标志物和治疗靶点。