Computational identification of MiRNA-7110 from pulmonary arterial hypertension (PAH) ESTs: a new microRNA that links diabetes and PAH,Hypertension Research

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Computational identification of MiRNA-7110 from pulmonary arterial hypertension (PAH) ESTs: a new microRNA that links diabetes and PAH
Hypertension Research ( IF 4.3 ) Pub Date : 2019-12-02 , DOI: 10.1038/s41440-019-0369-5
Jayapriya Johnson ₁ , Ganesh Lakshmanan ₂ , Biruntha M ₃ , Vidhyavathi R M ₄ , Kohila Kalimuthu ₅ , Durairaj Sekar ₁

Affiliation

Pulmonary arterial hypertension (PAH) is a chronic cardiopulmonary disorder arising from the vasoconstriction of arteries wherein the blood flow is restricted, resulting in increased blood pressure [1]. PAH is characterized by increased vascular resistance, reduced apoptosis in endothelial cells and cardiac hypertrophy, which leads to right ventricular breakdown of the heart and finally leads to patient death [2]. Although numerous strategies have been improved for PAH control, including early diagnosis, surgery and the development of newer treatment methods, the treatment options for PAH are still suboptimal, resulting in a poor survival rate [2, 3]. MicroRNAs (miRNAs) are short, noncoding RNA molecules that regulate gene expression in cells by targeting the 3′ untranslated regions of their cognate mRNAs [4, 5]. Interestingly, miRNAs are involved in cell proliferation, differentiation, apoptosis and other cellular developmental processes [6]. There are several studies linking the aberrant expression and deregulation of miRNAs with vascular pathophysiological conditions that include immune and inflammatory responses, aging, cancer and cardiovascular diseases. Fortunately, miRNAs are more stable than mRNAs in cells and are readily detected in plasma, platelets, red blood cells and other nucleated cells [6], suggesting that miRNAs may be used as biomarkers and therapeutic molecules for PAH [7]. The causes of PAH range from idiopathic disease to multiple disorders involving vascular pathologies. It has been reported that there is a strong relationship between diabetes and PAH since they share most of the common cellular pathways for disease progression [8, 9]. Therefore, the identification of common molecular target(s) that link these two diseases is necessary for a better understanding of their pathogenesis and may open a gateway for new treatment options and disease management. On the other hand, expressed sequence tags (ESTs) are fragments of mRNA sequences derived from randomly selected cDNA clones. ESTs serve as a landmark for gene identification and the verification of gene predictions in genomic mapping. Furthermore, ESTs have been indicated to be an effective tool for gene discovery across various methods. In our previous study, miRNA-7110 was identified in human diabetes mellitus ESTs and is highly expressed in type 1 diabetes mellitus, suggesting that it may serve as a prognostic, diagnostic or therapeutic target for diabetes mellitus [10]. Our hypothesis suggests that miR-7110 may also be present in PAH ESTs and might be responsible for inducing or suppressing disease progression. To test this hypothesis, we evaluated the available human PAH ESTs extracted from the NCBI EST database for miR-7110 through a computational approach. Fortunately, we identified the same miRNA, miR-7110, in PAH ESTs. The methods for the identification of miR-7110 were carried out as described by Priyanka et al. [10] and Bai et al. [11]. The source sequences, length of the precursor sequences, minimum folding energy and A+U content of the predicted miRNA are shown in Table 1. Secondary structural analysis of the pre-miRNA-related sequence of the noncoding ESTs * Durairaj Sekar duraimku@gmail.com

中文翻译：

肺动脉高压 (PAH) ESTs 中 MiRNA-7110 的计算鉴定：一种连接糖尿病和 PAH 的新 microRNA

肺动脉高压(PAH)是一种慢性心肺疾病，由动脉血管收缩引起，其中血流受限，导致血压升高[1]。PAH的特点是血管阻力增加、内皮细胞凋亡减少和心脏肥大，导致心脏右心室衰竭，最终导致患者死亡[2]。尽管 PAH 控制的许多策略已经得到改进，包括早期诊断、手术和开发新的治疗方法，但 PAH 的治疗方案仍然不理想，导致生存率较低 [2, 3]。MicroRNA (miRNA) 是短的非编码 RNA 分子，通过靶向其同源 mRNA 的 3' 非翻译区来调节细胞中的基因表达 [4, 5]。有趣的是，miRNAs 参与细胞增殖、分化、凋亡和其他细胞发育过程[6]。有几项研究将 miRNA 的异常表达和失调与血管病理生理状况联系起来，包括免疫和炎症反应、衰老、癌症和心血管疾病。幸运的是，miRNA 在细胞中比 mRNA 更稳定，并且很容易在血浆、血小板、红细胞和其他有核细胞中检测到 [6]，这表明 miRNA 可以用作 PAH 的生物标志物和治疗分子 [7]。PAH 的病因范围从特发性疾病到涉及血管病变的多种疾病。据报道，糖尿病和 PAH 之间有很强的关系，因为它们共享疾病进展的大多数常见细胞途径 [8, 9]。所以，确定连接这两种疾病的共同分子靶点对于更好地了解其发病机制是必要的，并可能为新的治疗选择和疾病管理打开大门。另一方面，表达序列标签 (EST) 是来自随机选择的 cDNA 克隆的 mRNA 序列片段。EST 作为基因鉴定和基因组图谱中基因预测验证的里程碑。此外，EST 已被证明是通过各种方法进行基因发现的有效工具。在我们之前的研究中，miRNA-7110 在人类糖尿病 EST 中得到鉴定，并且在 1 型糖尿病中高度表达，表明它可以作为糖尿病的预后、诊断或治疗靶点 [10]。我们的假设表明 miR-7110 也可能存在于 PAH EST 中，并且可能负责诱导或抑制疾病进展。为了验证这一假设，我们通过计算方法评估了从 NCBI EST 数据库中提取的 miR-7110 可用的人类 PAH EST。幸运的是，我们在 PAH EST 中鉴定了相同的 miRNA，miR-7110。鉴定 miR-7110 的方法按照 Priyanka 等人的描述进行。[10] 和白等人。[11]。预测miRNA的源序列、前体序列长度、最小折叠能和A+U含量见表1。非编码ESTs的pre-miRNA相关序列的二级结构分析* Durairaj Sekar duraimku@gmail。电脑我们通过计算方法评估了从 NCBI EST 数据库中提取的 miR-7110 可用的人类 PAH EST。幸运的是，我们在 PAH EST 中鉴定了相同的 miRNA，miR-7110。鉴定 miR-7110 的方法按照 Priyanka 等人的描述进行。[10] 和白等人。[11]。预测miRNA的源序列、前体序列长度、最小折叠能和A+U含量见表1。非编码ESTs的pre-miRNA相关序列的二级结构分析* Durairaj Sekar duraimku@gmail。电脑我们通过计算方法评估了从 NCBI EST 数据库中提取的 miR-7110 可用的人类 PAH EST。幸运的是，我们在 PAH EST 中鉴定了相同的 miRNA，miR-7110。鉴定 miR-7110 的方法按照 Priyanka 等人的描述进行。[10] 和白等人。[11]。预测miRNA的源序列、前体序列长度、最小折叠能和A+U含量见表1。非编码ESTs的pre-miRNA相关序列的二级结构分析* Durairaj Sekar duraimku@gmail。电脑 [10] 和白等人。[11]。预测miRNA的源序列、前体序列长度、最小折叠能和A+U含量见表1。非编码ESTs的pre-miRNA相关序列的二级结构分析* Durairaj Sekar duraimku@gmail。电脑 [10] 和白等人。[11]。预测miRNA的源序列、前体序列长度、最小折叠能和A+U含量见表1。非编码ESTs的pre-miRNA相关序列的二级结构分析* Durairaj Sekar duraimku@gmail。电脑

更新日期：2019-12-02

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