长链非编码RNA HOTAIR的分析及在黑色素瘤致病过程中互作分子的预测

doi:10.11843/j.issn.0366-6964.2017.08.006

摘要/Abstract

摘要：

旨在通过生物信息学分析，预测与HOTAIR相互作用的转录因子、蛋白质及miRNA，为阐明黑色素瘤致病的分子机理提供研究方向，为设计新的药物提供靶标和治疗黑色素瘤提供理论基础。本试验在UCSC数据库中下载8个物种的HOTAIR序列，通过MEGA4.0构建系统进化树；运用lncRNAtor等数据库对长链非编码RNA HOTAIR的上游调控因子，互作的miRNA及相关蛋白进行分析；利用NONCODE和lncDisease等数据库分析HOTAIR在各组织的表达模式及与HOTAIR相关的疾病；使用TargetScan软件在线预测与黑色素瘤紧密相关的一些基因的靶标miRNAs；运用Cytoscape3.2.0软件绘制miRNA-HOTAIR-黑色素瘤相关基因的分子调控网络图。结果表明，HOTAIR定位于人类12q13.13染色体上HOXC11与HOXC12基因的54 356 092~54 368 740 nt位点之间，并且HOTAIR在不同的物种之间具有一定的保守性。HOTAIR在不同的细胞中受到多种调控因子的调控。HOTAIR特异表达于各个组织，在睾丸中的表达量明显高于其他组织，而在肺和卵巢中的表达量明显低于其他组织。GO功能分析发现，HOTAIR的靶基因参与细胞凋亡、DNA复制、转录调控等生物学过程，表明HOTAIR在癌症和一些人类疾病的病理及生理学过程中发挥着重要的作用。在HOTAIR的互作分析中发现，HOTAIR与miR-217、miR-203和miR-194等均有互作位点。结果显示，在黑色素瘤中，HOTAIR可能会与MITF和NKX3-1等黑色瘤关键基因竞争性结合miR-217、miR-203和miR-194，从而实现HOTAIR对黑色素瘤的调控，但还需要进一步的试验证明。GO功能分析和KEGG通路分析发现HOTAIR的表达水平与肿瘤的转移、复发以及预后紧密相关，结合一些转录因子对HOTAIR的调控为肿瘤的治疗提供一定的理论基础。

Abstract:

This study aimed to predict the transcription factor, protein and miRNA interacting with HOTAIR by bioinformatics, provide research direction for understanding the molecular mechanism of melanoma pathogenesis, and provide a target for designing new drugs and a theoretical basis for treating the melanoma. In this study, we downloaded HOTAIR sequences of 8 species from UCSC database, established phylogenetic tree by MEGA4.0. We used lncRNAtor and other databases to analyze the upstream regulatory factors, miRNA interacting with HOTAIR and related proteins. The expression patterns of HOTAIR in various tissues and the diseases associated with HOTAIR were analyzed via NONCODE and lncDisease databases. Some of the target miRNAs related to melanoma were predicted by TargetScan software. The molecular regulatory network of miRNA-HOTAIR-melanoma-associated genes was drew using Cytoscape3.2.0 software. The results showed that HOTAIR was located on human 12q13.13 chromosome between HOXC11 and HOXC12 genes at 54 356 092-54 368 740 nt. The HOTAIR was conservative among different species. HOTAIR was regulated by 27 regulatory factors in 18 different cells. HOTAIR was expressed in various tissues, and the expression in testis was higher than that in other tissues, but the expression in lung and ovary was lower than that in other tissues. GO analysis showed that the target genes of HOTAIR involved in cell apoptosis, DNA replication, transcription and other biological processes, which showed that HOTAIR played important roles in the process of pathology and physiology of cancer and some human diseases. The interaction analysis showed that there were interaction sites in miR-217, miR-203 and miR-194 with HOTAIR. In melanoma, HOTAIR may compete with MITF and NKX3-1 to miR-217, miR-203 and miR-194. GO function analysis and KEGG pathway analysis show that the expression level of HOTAIR was closely related to tumor metastasis, recurrence and prognosis, combined with the regulation of transcription factors to HOTAIR, which provide a theoretical basis for treatment of tumors.

中图分类号:

S813.1

李园, 刘文艳, 蔡永强, 张利环, 李宏, 朱芷葳. 长链非编码RNA HOTAIR的分析及在黑色素瘤致病过程中互作分子的预测[J]. 畜牧兽医学报, 2017, 48(8): 1424-1435.

LI Yuan, LIU Wen-yan, CAI Yong-qiang, ZHANG Li-huan, LI Hong, ZHU Zhi-wei. Analysis of Long Non-coding RNA HOTAIR and Prediction of Its Interaction Molecules in Melanoma Pathogenesis[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2017, 48(8): 1424-1435.

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