Recurrent cis-SAGe chimeric RNA, D2HGDH-GAL3ST2, in prostate cancer.
Recurrent cis-SAGe chimeric RNA, D2HGDH-GAL3ST2, in prostate cancer.
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DOI：
10.1016/j.canlet.2016.06.013
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发表时间：
2016-09-28
期刊：
影响因子：
9.7
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Qin F;Song Z;Chang M;Song Y;Frierson H;Li H
相邻基因在相同方向上转录可以通过顺式剪接（cis-SAGe）形成嵌合rna。在此之前，我们在前列腺癌细胞系中报道了16个新的顺式- sage嵌合体，并对来自中国患者的14对正常和肿瘤样本进行了计算机验证。然而，这些融合是否存在于不同的人群中，以及它们的临床意义，仍然不清楚。为了进行研究，我们开发了一个生物信息学管道，使用修饰的Spliced Transcripts Alignment To a Reference （STAR）在计算机上同时量化这些融合rna。从TCGA的100对正常和前列腺癌样本的RNA-Seq数据中，我们发现大多数融合不是针对癌症的。然而，D2HGDH-GAL3ST2在癌症样本中更为常见，并且似乎在非裔美国人群体中富集。通过我们自己的收集和商业来源的进一步验证，没有在29个正常前列腺样本中检测到这种融合RNA，但在93个前列腺癌样本中的19个中检测到这种融合RNA。它在晚期癌症中更常被发现，这表明它在癌症进展中起作用。一致地，沉默这种融合导致细胞增殖率和细胞运动性显著降低。
Neighboring genes transcribing in the same direction can form chimeric RNAs via cis-splicing (cis-SAGe). Previously, we reported 16 novel cis-SAGe chimeras in prostate cancer cell lines, and performed in silico validation on 14 pairs of normal and tumor samples from Chinese patients. However, whether these fusions exist in different populations, as well as their clinical implications, remains unclear. To investigate, we developed a bioinformatics pipeline using modified Spliced Transcripts Alignment to a Reference (STAR) to quantify these fusion RNAs simultaneously in silico. From RNA-Seq data of 100 paired normal and prostate cancer samples from TCGA, we find that most fusions are not specific to cancer. However, D2HGDH-GAL3ST2 is more frequently seen in cancer samples, and seems to be enriched in the African American group. Further validation with our own collection as well as from commercial sources did not detect this fusion RNA in 29 normal prostate samples, but in 19 of 93 prostate cancer samples. It is more frequently detected in late stage cancer, suggesting a role in cancer progression. Consistently, silencing this fusion resulted in dramatic reduction of cell proliferation rate and cell motility.
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