同济大学Nature子刊解析癌症长链非编码RNA调控网络

同济大学生命科学与技术学院刘小乐教授课题组3月15日在Nature子刊《Nature Communications》杂志发表关于前列腺癌中基于长链非编码RNA调控网络的重要研究成果“Integrative analyses reveal a long non-coding RNA-mediated sponge regulatory network in prostate cancer”。

长链非编码RNA是一类长度大于200bp且没有蛋白编码能力的RNA分子。前期研究表明此类RNA分子可以通过自己内部之间和在外部跟可编码蛋白RNA竞争结合microRNA来构成一个复杂的调控网络。刘小乐课题组利用生物信息和实验手段相结合的方式在前列腺癌细胞中对该网络进行了深入研究。研究人员发现这些长链非编码RNA可以利用这个网络对一些关键致癌基因进行调控，并利用数据整合挖掘的手段构建出此调控网络结构图，并进一步证实了该网络中的两个长链非编码RNA，TUG1和之前功能未知的ENST00000519077可以通过次网络来调控癌基因pTEN进而实现抑制肿瘤细胞生长。研究人员还发现该长链非编码RNA的调控网络还跟RNA分子在细胞中的位置息息相关，例如分布于细胞核中和细胞质中TUG1对于癌基因的调控作用并不相同。

通过本研究中，研究人员在前列腺癌细胞证实了基于长链非编码RNA的新颖调控网络，为进一步揭示癌细胞内的基因互做网络打下了基础。该项目是生物信息学与生物实验紧密结合的产物，同时也是个国际合作项目，其中课题设计、生物信息学分析等工作由刘小乐课题组博士后杜舟在同济完成，实验验证等部分工作在美国哈佛大学的Dana-Farber癌症研究中心完成。该项目受到了国家科技部和自然基金委的共同资助。

原文摘要：

Integrative analyses reveal a long non-coding RNA-mediated sponge regulatory network in prostate cancer
Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours. We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of pTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (pRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA.