Wei Yunzhen, Yan Zichuang, Wu Cheng, Zhang Qiang, Zhu Yinling, Li Kun, Xu Yan
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Oncotarget. 2017 Aug 3;8(42):71430-71446. doi: 10.18632/oncotarget.19864. eCollection 2017 Sep 22.
Accumulating evidences indicate that cancer-related lncRNAs occur frequent somatic copy number alternation (SCNA). Although individual SCNA lncRNAs have been implicated in tumor biology, their regulatory mechanism has not been assessed in a systematic way. In order to explore the expression characteristics and biological functions of SCNA lncRNAs in cancer, we built a computational framework based on lncRNA expression profiles, lncRNA copy numbers and dosage sensitivity score (DSS). First, we found that the lncRNAs with different DSS were involved in distinct biological processes, while those with the same DSS had similar functions. Second, some of the lncRNAs participated in the progression and metastasis of lung adenocarcinoma (LUAD) through cis-acting regulation. In lncRNA-TF-mRNA network, lncRNAs interacted with 4 TFs and affected the immune system, and further influenced LUAD progression. Third, competing endogenous RNA network analysis inferred that lncRNA ENSG00000240990 competed with HOXA10 to absorb hsa-let-7a/b/f/g-5p and affected patient prognosis in LUAD. Last but not least, by integrating target information of miRNA we also provided a new perspective for the discovery of potential small molecule drugs. In summary, we systematically analyzed the regulatory role of SCNA lncRNAs. This work may facilitate cancer research and serve as the basis for future efforts to understand the role of SCNA lncRNAs, develop novel biomarkers and improve knowledge of tumor biology.
越来越多的证据表明，与癌症相关的长链非编码RNA（lncRNA）经常发生体细胞拷贝数改变（SCNA）。尽管个别SCNA lncRNA已被证明与肿瘤生物学有关，但其调控机制尚未得到系统评估。为了探索SCNA lncRNA在癌症中的表达特征和生物学功能，我们基于lncRNA表达谱、lncRNA拷贝数和剂量敏感性评分（DSS）构建了一个计算框架。首先，我们发现具有不同DSS的lncRNA参与不同的生物学过程，而具有相同DSS的lncRNA具有相似的功能。其次，一些lncRNA通过顺式作用调控参与肺腺癌（LUAD）的进展和转移。在lncRNA-TF-mRNA网络中，lncRNA与4种转录因子（TF）相互作用并影响免疫系统，进而影响LUAD的进展。第三，竞争性内源性RNA网络分析推断lncRNA ENSG00000240990与HOXA10竞争以吸附hsa-let-7a/b/f/g-5p，并影响LUAD患者的预后。最后但同样重要的是，通过整合miRNA的靶标信息，我们还为发现潜在的小分子药物提供了新的视角。总之，我们系统地分析了SCNA lncRNA的调控作用。这项工作可能有助于癌症研究，并为未来理解SCNA lncRNA的作用、开发新型生物标志物以及增进对肿瘤生物学的认识奠定基础。
