mi-RNA129-1 and mi-RNA24-2 as regulators of over-expressed genes in lung typical carcinoid tumors: Potential targets for molecular therapy

Abbas-Chakhtoura Jad, Chinchilla-Monge Ricardo, Mora-Rodriguez Rodrigo
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Abstract

Lung carcinoid tumors are malignant neuroendocrine neoplasms that account for less than 2% of all lung malignancies and include two histological types: typical and atypical carcinoid tumors. Typical carcinoid tumors do not include areas of necrosis and show less than 2 mitotic figures within 10 high grade fields. On the molecular level, carcinoid tumors present alterations in gene MEN1 as well as a high expression of genes ASCL1 and EIF1AX. We report a systems biology approach using BioNetUCR and Copasi in addition to Cytoscape to identify mi-RNA regulators of the most important altered genes in typical pulmonary carcinoid tumors. The final adjusted and reduced interaction network of our genes of interest included: 3 genes 12 transcription factors and 7 mi-RNAs, leading to a total of 22 nodes and 53 edges. Analysis with Copasi showed that MIR24-2 regulates the expression of MEN1 and MIR129-1 regulates the expression of AIF1AX. Those mi-RNAs could be potential targets for molecular therapy in patients with typical carcinoid tumor of lung.
mi-RNA129-1和mi-RNA24-2作为肺典型类癌过度表达基因的调节因子:分子治疗的潜在靶点
肺类癌是一种恶性神经内分泌肿瘤,占所有肺部恶性肿瘤的不到2%,包括典型和非典型两种组织学类型。典型的类癌不包括坏死区域,在10个高分级野中显示少于2个有丝分裂象。在分子水平上,类癌肿瘤表现为MEN1基因的改变以及ASCL1和EIF1AX基因的高表达。我们报告了一种系统生物学方法,使用BioNetUCR和Copasi以及Cytoscape来鉴定典型肺类癌中最重要的改变基因的mi-RNA调节因子。我们最终调整和减少的目标基因相互作用网络包括:3个基因12个转录因子和7个mi-RNAs,共22个节点和53个边。Copasi分析显示,MIR24-2调控MEN1的表达,MIR129-1调控AIF1AX的表达。这些mir - rna可能成为典型肺类癌患者分子治疗的潜在靶点。
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