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Transcription-Mediated Chimeric RNAs in Prostate Cancer: Time to Revisit Old Hypothesis?

机译:前列腺癌中转录介导的嵌合RNA:重新审视旧的假设吗?

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摘要

Chromosomal rearrangements and fusion genes play important roles in tumor development and progression. Four high-frequency prostate cancer-specific fusion genes were recently reported in Chinese cases. We attempted to confirm one of the fusion genes, USP9Y-TTTY15, by reverse transcription PCR, but detected the presence of the USP9Y-TTTY15 fusion transcript in cancer samples, nonmalignant prostate tissues, and normal tissues from other organs, demonstrating that it is a transcription-induced chimeric RNA, which is commonly produced in normal tissues. In 105 prostate cancer samples and case-matched adjacent nonmalignant tissues, we determined the expression level of USP9Y-TTTY15 and a previously reported transcription-induced chimeric RNA, SLC45A3-ELK4. The expression levels of both chimeric RNAs vary greatly in cancer and normal cells. USP9Y-TTTY15 expression is neither higher in cancer than adjacent normal tissues, nor correlated with features of advanced prostate cancer. Although the expression level of SLC45A3-ELK4 is higher in cancer than normal cells, and a dramatic increase in its expression from normal to cancer cells is correlated with advanced disease, its expression level in cancer samples alone is not correlated with any clinical parameters. These data show that both chimeric RNAs contribute less to prostate carcinogenesis than previously reported.
机译:染色体重排和融合基因在肿瘤的发生和发展中起重要作用。最近在中国病例中报道了四个高频前列腺癌特异性融合基因。我们试图通过逆转录PCR确认融合基因之一USP9Y-TTTY15,但在癌症样品,非恶性前列腺组织和其他器官的正常组织中检测到USP9Y-TTTY15融合转录本的存在,表明它是一种转录诱导的嵌合RNA,通常在正常组织中产生。在105个前列腺癌样本和与病例匹配的相邻非恶性组织中,我们确定了USP9Y-TTTY15和先前报道的转录诱导的嵌合RNA SLC45A3-ELK4的表达水平。两种嵌合RNA的表达水平在癌症和正常细胞中差异很大。 USP9Y-TTTY15在癌症中的表达既不高于邻近的正常组织,也不与晚期前列腺癌的特征相关。尽管SLC45A3-ELK4在癌症中的表达水平高于正常细胞,并且其从正常细胞到癌细胞的表达急剧增加与晚期疾病相关,但仅在癌症样本中其表达水平与任何临床参数均不相关。这些数据表明,两种嵌合RNA对前列腺癌发生的贡献均比以前报道的少。

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