关键词: Chimeric RNA Cis-splicing DUS4L-BCAP29 Gastric Prostate

Mesh : Cell Line, Tumor Gene Fusion Gene Knockdown Techniques Humans Membrane Proteins / genetics Organ Specificity Oxidoreductases / genetics RNA / genetics RNA Interference Reverse Transcriptase Polymerase Chain Reaction Transcription, Genetic

来  源:   DOI:10.1007/978-1-4939-9904-0_19

Abstract:
Traditional gene fusions are involved in the development of various neoplasias. DUS4L-BCAP29, a chimeric fusion RNA, has been reported to be a cancer-related fusion in prostate and gastric cancers. This chimeric RNA is believed to play a tumorigenic role. Here, we showed that the DUS4L-BCAP29 fusion transcript exists in a variety of normal tissues. It is also present in noncancerous epithelial and fibroblast cell lines. Quantitatively, the fusion transcript has a similar expression level in noncancerous gastric and prostate cell lines and tissues to its expression in cancerous cell lines and tissues. Previously, a loss-of-function approach was used to report a probable functionality for this fusion. However, this approach is not sufficient to prove such functionality. Alternatively, a gain-of-function approach showed that overexpression of DUS4L-BCAP29 promotes cell growth and motility, even in noncancerous cell lines. Finally, we provide further evidence that the fusion transcript is a product of cis-splicing between adjacent genes. In summary, we believe that in contrast to traditional gene fusions, DUS4L-BCAP29 cannot be used as a cancer biomarker. Instead, it is a fusion transcript that exists in normal physiology and its progrowth effect is not unique to cancer situations.
摘要:
传统的基因融合参与各种肿瘤的发展。DUS4L-BCAP29,一种嵌合融合RNA,据报道,前列腺癌和胃癌是与癌症相关的融合。这种嵌合RNA被认为发挥致瘤作用。这里,我们表明DUS4L-BCAP29融合转录本存在于多种正常组织中。它也存在于非癌上皮和成纤维细胞系中。定量地,融合转录本在非癌胃和前列腺细胞系和组织中的表达水平与其在癌细胞系和组织中的表达水平相似。以前,使用功能缺失方法报告此融合的可能功能.然而,这种方法不足以证明这种功能。或者,获得功能的方法表明,过度表达DUS4L-BCAP29促进细胞生长和运动,甚至在非癌细胞系中。最后,我们提供了进一步的证据,证明融合转录物是相邻基因之间顺式剪接的产物。总之,我们相信与传统的基因融合相比,DUS4L-BCAP29不能用作癌症生物标志物。相反,它是存在于正常生理学中的融合转录物,其促生长作用并非癌症情况所独有。
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