基于基因功能相似性预测小分子药物与lncRNA的相关关系  

Predicting associations between small molecules and lncRNAs based on functional similarity

作　　者：吕莹丽 王世缘[1] 闫琰 宁尚伟[1] 付强 杨磊[1] 

机构地区：[1]哈尔滨医科大学生物信息科学与技术学院,黑龙江哈尔滨150081

出　　处：《哈尔滨医科大学学报》2017年第5期404-408,共5页Journal of Harbin Medical University

基　　金：黑龙江省教育厅科学技术研究项目(12541524)

摘　　要：目的开发靶向表达失调的非编码RNA的小分子药物,以提供一种全新的癌症治疗策略。方法通过整合小分子与lncRNA的靶基因数据,基于基因功能相似性,构建小分子与lncRNA关联关系模型,预测小分子潜在相关的lncRNAs,对显著相关的小分子-lncRNA关联网络进行拓扑性和功能性分析,依据数据库和文本挖掘评价预测的小分子-lncRNA关系。结果得到280个小分子与79个lncRNA之间805对显著相关关系;网络中小分子节点呈现幂律分布;同一小分子靶向的lncRNA对共享疾病(5.0995×10-6),同一lncRNA关联的小分子对共享疾病(3.1577×10-28)和副作用(2.1668×10-67),并具有相似的化学结构(2.053×10-62);在慢性骨髓白血病、恶性胃肠道间质瘤中,MEG3、H19、HOTAIR与伊马替尼存在潜在关联;FENDRR与Glisoxepide在糖尿病肾病治疗中存在潜在关联。结论基于基因功能相关性为预测小分子相关lncRNAs提供了一条新途径,促进了癌症靶向治疗的发展。Objective To identif small molecule drug （SM） that target dysregulated lncRNAs to provide new insight into cancer therapy. Methods The SM-LncRNA association network was established based on functional similarity of genes by integrating target gene database of SM and LncRNA. LneRNAs associated to each of the SMs were predicted and the SM-LncRNA association network was performed topological and functional analysis. Furthelanore, the predicted SM-LncRNA associations were evaluated using database and literature reviews. Results The SM-miRNA association network involved 804 pairs between 280 SMs and 79 LncRNAs. The degree distribution of SMs was power law. The lncRNAs that were linked to the same SMs shared more common diseases （2. 053 × 10-62）. The SMs that were connected with the same lncRNAs tended to share common diseases （5.0995 × 10-6） and side effects （3. 1577 × 10-28） and had similar chemical structures （2. 1668 × 10-67 ） . MEG3 and H19 involved in chronic myeloid leukemia and HOTAIR involved in malignant gastrointestinal stromal tumor were speculated with imatinib. FENDRR and Glisoxepide had potential association in the treatment of diabetic nephropathy. Conclusion The method of functional similarity of genes might pave a new way for lncRNA-associated therapy and would improve the development of targeting therapy.

关 键 词：小分子 lncRNA 关联关系 功能相似性 

分 类 号：Q811.4[生物学—生物工程]