In-Silico Target Prediction for Hsa-Mir-27a and Identification of Genes Involved In Breast Cancer

IF 0.1 4区 生物学 Q4 GENETICS & HEREDITY
A. Shah
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引用次数: 1

Abstract

MicroRNAs (miRNAs) are key gene regulators in all living organisms. They play an important role in various diseases including breast cancer (BC). Mutations within MIR27a gene have been linked with various types of cancers including breast cancer. Several tools are being used to identify potential targets for crucial miRNA genes. In the present study, online target prediction tools were used to investigate target genes that may be regulated by the mature form of MIR27a (hsa-mir-27a-3p and has-mir-27a-5p). A total of 52 target genes were found for hsa-mir-27a while for hsa-mir-27a-5p determined 45 targets. These target genes were further explored for their potential role in BC. It was found that the target genes are involved in vital biological processes in cancer progression and development. In conclusion, MIR27a may regulate several genes that are vital for BC development and progression. MIR27a may act as a promising new biomarker for anti-breast cancer therapy. *Address for correspondence: Aftab Ali Shah Department of Biotechnology, University of Malakand, Chakdara, Pakistan E-mail: aftabuom@gmail.com INTRODUCTION MicroRNAs (miRNAs) are small, highly conserved noncoding short (19-24 nt) RNA molecules that control gene expression post-transcriptionally, either by degradation of target mRNAs or by inhibition of protein translation. It is already known that miRNAs have a significant role in crucial biological pathways (Oliveto et al. 2017) More than fifty percent of all genes in the human genome are known to be regulated by miRNAs (Keller et al. 2014). Recently it is shown that abnormal expression of miRNAs is related to a broad range of human diseases (Chen et al. 2018; Li and Kowdley 2012). A large number of miRNAs have been discovered by cloning and size-fractionated RNA techniques. The researchers’ previous studies have shown altered expression profile of selected miRNA in caloric metabolism and gastric cancer by using whole genome miRNA profiling studies using blood samples from human and related knockout mouse models (Shah et al. 2013; Shah et al. 2012; Shah et al. 2011). MIR27a is thought to be an oncomir promoting tumor growth and metastasis. It has been reported to be a marker for breast cancer progression and patient survival (Zhao et al. 2016). MiR-27a is involved in the modulation of growth, angiogenesis and metastasis of BC and gastric cancer cells (Ding et al. 2017; Zhou et al. 2016a; Tang et al. 2014). Targets genes of the majority of the miRNA are not known, but the predicted limit is from a single to hundreds of genes for a certain miRN As, which is based on target estimation by applying an array of bioinformatics methods. The biogenesis of miRNAs is a highly regulated process, and alteration in their regulation is linked with many diseases in human (Chen et al. 2018; Ding et al. 2017; Ha and Kim 2014). Expression of miRNAs is tissue-specific and also influenced by different developmental stages. Hence, miRNAs exhibiting abnormal expression levels in the situation of certain diseases are of great importance as therapeutic targets. As only a limited regulatory target is known, predicting and validating miRNA targets is one of the major hurdles in understanding miRNA biology. Due to diversity in miRNAs and difficulty in experimental identification of target genes, the specific function of most miRNAs is not known. It is necessary to find their target mRNAs to explore their post-transcriptional regulating properties and associations for ailments and diagnostics. Bioinformatics tools were used to predict target mRNAs for MIR27a. Int J Hum Genet, 19(1): 12-21 (2019) DOI: 10.31901/24566330.2019/19.01.683 © Kamla-Raj 2019 PRINT: ISSN 0972-3757 ONLINE: ISSN 2456-6330 MIR27A REGULATES BREAST CANCER PROGRESSION 13
Hsa-Mir-27a的原位靶向预测及癌症相关基因的鉴定
微小RNA(miRNA)是所有生物体中的关键基因调节因子。它们在包括癌症(BC)在内的各种疾病中发挥着重要作用。MIR27a基因的突变与包括癌症在内的各种癌症有关。一些工具正在被用来识别关键miRNA基因的潜在靶点。在本研究中,使用在线靶点预测工具来研究可能由成熟形式的MIR27a(hsa-mir-27a-3p和has-mir-27a-5p)调节的靶基因。共发现52个hsa-mir-27a靶基因,而hsa-mir27a-5p确定了45个靶基因。这些靶基因在BC中的潜在作用被进一步探索。研究发现,靶基因参与了癌症进展和发展的重要生物学过程。总之,MIR27a可能调节对BC发育和进展至关重要的几个基因。MIR27a可能作为一种有前景的抗乳腺癌症治疗新生物标志物*通信地址:Aftab Ali Shah巴基斯坦Chakdara马拉坎大学生物技术系电子邮件:aftabuom@gmail.com引言微小RNA(miRNA)是一种小的、高度保守的非编码短(19-24nt)RNA分子,通过降解靶mRNA或抑制蛋白质翻译,在转录后控制基因表达。众所周知,miRNA在关键的生物途径中发挥着重要作用(Oliveto等人,2017)已知人类基因组中50%以上的基因受到miRNA的调控(Keller等人,2014)。最近有研究表明,miRNA的异常表达与广泛的人类疾病有关(Chen等人,2018;李和Kowdley,2012年)。通过克隆和大小分级RNA技术已经发现了大量的miRNA。研究人员先前的研究表明,通过使用人类和相关敲除小鼠模型的血液样本进行全基因组miRNA谱研究,选定的miRNA在热量代谢和癌症中的表达谱发生了变化(Shah等人2013;Shah等人2012;Shah等人2011)。MIR27a被认为是一种促进肿瘤生长和转移的肿瘤学家。据报道,它是癌症进展和患者生存的标志物(赵等人,2016)。MiR-27a参与调节BC和癌症细胞的生长、血管生成和转移(Ding et al.2017;Zhou et al.2016a;Tang et al.2014)。大多数miRNA的靶基因尚不清楚,但预测的极限是某一miRNA的单个到数百个基因,这是基于应用一系列生物信息学方法对靶基因的估计。miRNA的生物发生是一个高度调节的过程,其调节的改变与人类的许多疾病有关(Chen等人,2018;丁等人2017;Ha和Kim,2014)。miRNA的表达是组织特异性的,也受到不同发育阶段的影响。因此,在某些疾病中表现出异常表达水平的miRNA作为治疗靶点具有重要意义。由于目前已知的调控靶点有限,预测和验证miRNA靶点是理解miRNA生物学的主要障碍之一。由于miRNA的多样性和靶基因的实验鉴定困难,大多数miRNA的具体功能尚不清楚。有必要找到它们的靶mRNA,以探索它们的转录后调节特性以及与疾病和诊断的相关性。生物信息学工具用于预测MIR27a的靶mRNAs。Int J Hum Genet,19(1):12-21(2019)DOI:10.31901/245663.2019/19.01.683©Kamla Raj 2019印刷:ISSN 0972-3757在线:ISSN 2456-6330 MIR27A调节乳腺癌进展13
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