Cloning and Functional Characterization of a Novel Long Non-coding RNA Gene Associated With Hepatocellular Carcinoma
Cloning and Functional Characterization of a Novel Long Non-coding RNA Gene Associated With Hepatocellular Carcinoma
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DOI：
10.3724/sp.j.1206.2012.00613
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发表时间：
2014
影响因子：
0.3
通讯作者：
Gong Zj;Ming Zhou;Peng Sp;J. Ma;Xiaoyan Li;Hongbin Huang;Hongbin Huang;Y. Li;Xiaoling Li;H. Bo;Zeng Zy;Strong;Gui-yuan Li;Xiang Jj;W. Xiong;F. Wei;Zhang Wl;Liao Qj;K. Tang;Song Yl
中科院分区：
文献类型：
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作者：
Gong Zj;Ming Zhou;Peng Sp;J. Ma;Xiaoyan Li;Hongbin Huang;Hongbin Huang;Y. Li;Xiaoling Li;H. Bo;Zeng Zy;Strong;Gui-yuan Li;Xiang Jj;W. Xiong;F. Wei;Zhang Wl;Liao Qj;K. Tang;Song Yl
最近，我们利用基于下一代测序(NGS)技术的RNA测序(RNA-Seq)策略对肝细胞癌活检组织和正常肝组织的转录本进行了测序，在肝细胞癌活检组织中发现了位于染色体11q13.1上的几个相邻的高RNA-Seq信号峰，而在正常对照组织中没有发现。在这个染色体区域，还没有鉴定出特征基因，这意味着这些RNA-Seq峰可能代表一个或多个新基因。进一步的研究证实，这些RNA-Seq峰是由一个新基因转录的。通过克隆该新基因的全长，我们发现该新基因转录了多种剪接异构体，最长的异构体为3562个碱基。然后我们将12个具有代表性的RNA亚型存入国家生物技术信息中心(NCBI)的GenBank数据库，并为这些亚型创建了从KC136297到KC136308的GenBank ID。在该新基因的任何转录本中均未发现显著的开放阅读片段(ORF)，这意味着该基因可能编码长的非编码RNA(LncRNAs)。为了进一步阐明该基因潜在的转录调控机制，我们利用生物信息学工具从该基因上游序列预测了该启动子，发现在该基因转录起始点-719~-469bp处有一个潜在的启动子，启动子区域有7个Sp1、1个STAT5和1个Egr1转录因子结合位点。LncRNA基因在肝细胞癌发生发展中的分子机制值得进一步研究。
Recently, we sequenced the transcriptomes of a hepatocellular carcinoma biopsy and a normal liver tissue using the RNA-Sequencing(RNA-Seq) strategy based on the Next Generation Sequencing(NGS) technique, and identified several adjacent high RNA-Seq signal peaks on chromosome 11q13.1 in the hepatocellular carcinoma biopsy, while not in the normal control tissue. In this chromosome region, there is no characterized genes have been identified, implying that these RNA-Seq peaks may represent one or more novel genes. Further study was confirmed that these RNA-Seq peaks were transcribed by one novel gene. Through cloning the full length of this novel gene, we found that this novel gene transcribed many splicing isoforms, and the longest isoform is 3 562 bp. Then we deposited twelve representative RNA isoforms into the GenBank database of the National Center for Biotechnology Information(NCBI), and created the GenBank IDs from KC136297 to KC136308 for these isoforms. None significant open reading fragment(ORF) was found in any transcripts of this novel gene, implying that this gene may encodes long non-coding RNAs(lncRNAs). To further elucidate the potential transcriptional regulation mechanism of this lncRNA gene, we predicted the promoter from the upstream sequence of the lncRNA gene using bioinformatic tools, and found that there is one potential promoter in-719 to-469 bp from the transcript start site of the lncRNA gene, and there are seven Sp1, one STAT5 and one EGR1 transcription factor binding sites in the promoter region. The molecular mechanisms of the lncRNA gene in carcinogenesis and progression of hepatocellular carcinoma are worthful for further investigation.