Department of Surgery Oncology and Gastroenterology, University of Padova, Padua, Italy.
Clinica Chirurgica I, Azienda Ospedaliera Padova, Padua, Italy.
J Transl Med. 2019 May 14;17(1):153. doi: 10.1186/s12967-019-1907-2.
MicroRNA (miRNA) mediate post-transcriptional gene repression and are involved in a variety of human diseases, including cancer. Soft tissue sarcomas are rare malignancies with a variety of histological subtypes which may occur virtually anywhere in the human body. Leiomyosarcoma is one of the most common subtypes, shows a smooth muscle phenotype and its cancerogenesis is still unclear. The aim of our study was to investigate the potential role of miRNA differential expression in leiomyosarcoma development.
We first employed the Sarcoma microRNA Expression Database, a repository that describes the patterns of over 1000 miRNA expression in various human sarcoma types, to identify differentially expressed miRNA comparing leiomyosarcoma and smooth muscle samples. Subsequently, we identified putative target genes of those miRNAs with the TargetScan prediction tool. Finally, we evaluated whether the retrieved pool of putative targets was enriched in genes belonging to specific molecular pathways by means of the Enrichr analysis tool. Protein-protein network analysis was analyzed by means of the STRING web tool.
Out of 1120 miRNAs tested, the expression of 301 miRNAs was statistically significantly different between leiomyosarcoma and smooth muscle samples. The hypothetical targets could be predicted for 172 miRNAs. 438 genes were predicted to be the targets with high confidence (cumulative weighted context score cut-off level less than - 1.0) and analyzed for belonging to specific molecular pathways. Pathway analysis suggested that RNA Polymerase III, tRNA functions and synaptic neurotransmission (with special regard to dopamine mediated signaling) could be involved in leiomyosarcoma development.
Our results demonstrate that data mining of publicly available repositories can be useful to suggest molecular pathways underlying the pathogenesis of rare tumors such as leiomyosarcoma.
MicroRNA (miRNA) 介导转录后基因抑制，参与多种人类疾病，包括癌症。软组织肉瘤是一种罕见的恶性肿瘤，具有多种组织学亚型，几乎可以发生在人体的任何部位。平滑肌肉瘤是最常见的亚型之一，表现出平滑肌表型，其癌变机制尚不清楚。我们的研究目的是探讨 miRNA 差异表达在平滑肌肉瘤发生发展中的潜在作用。
我们首先使用 Sarcoma microRNA Expression Database，这是一个描述各种人类肉瘤类型中超过 1000 种 miRNA 表达模式的数据库，来识别平滑肌肉瘤和平滑肌样本之间差异表达的 miRNA。随后，我们使用 TargetScan 预测工具识别这些 miRNA 的潜在靶基因。最后，我们通过 Enrichr 分析工具评估检索到的潜在靶基因是否富集在特定分子途径的基因中。通过 STRING 网络工具分析蛋白质-蛋白质网络分析。
在测试的 1120 种 miRNA 中，有 301 种 miRNA 在平滑肌肉瘤和平滑肌样本之间的表达存在统计学差异。可以预测 172 种 miRNA 的假设靶基因。预测到 438 个基因是具有高置信度的靶基因（累积加权上下文评分截断水平小于-1.0），并分析其是否属于特定的分子途径。通路分析表明，RNA 聚合酶 III、tRNA 功能和突触神经传递（特别是多巴胺介导的信号转导）可能参与了平滑肌肉瘤的发生发展。
我们的研究结果表明，对公共可用数据库进行数据挖掘可以有助于提示罕见肿瘤（如平滑肌肉瘤）发病机制的分子途径。
