فایل ورد کامل شناسایی مکانیزم تعامل lncRNA-miRNA-mRNA در سرطان پستان بر اساس تجزیه و تحلیل بیوانفورماتیکی

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تعداد صفحات این فایل: ۲۲ صفحه

بخشی از مقاله انگلیسیعنوان انگلیسی:Identification of an lncRNAmiRNAmRNA interaction mechanism in breast cancer based on bioinformatic analysis~~en~~

Abstract

Non-coding RNAs serve important roles in regulating the expression of certain genes and are involved in the principal biological processes of breast cancer. The majority of studies have focused on defining the regulatory functions of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs), and few studies have investigated how lncRNAs and miRNAs are transcriptionally regulated. In the present study, based on the breast invasive carcinoma dataset from The Cancer Genome Atlas at cBioPortal, and using a bioinformatics computational approach, an lncRNA-miRNA-mRNA network was constructed. The network consisted of 601 nodes and 706 edges, which represented the complex web of regulatory effects between lncRNAs, miRNAs and target genes. The results of the present study demonstrated that miR-510 was the most potent miRNA controller and regulator of numerous target genes. In addition, it was observed that the lncRNAs PVT1, CCAT1 and linc00861 exhibited possible interactions with clinical biomarkers, including receptor tyrosine-protein kinase erbB-2, estrogen receptor and progesterone receptor, demonstrated using RNA-protein interaction prediction software. The network of lncRNA-miRNA-mRNA interactions will facilitate further experimental studies and may be used to refine biomarker predictions for developing novel therapeutic approaches in breast cancer.

Introduction

Breast cancer was the most common malignancy in women worldwide in 2015 (1). Breast cancer is a clinically heterogeneous disease, encompassing multiple histological types, pathological characteristics and a variety of clinical behaviors, making clinical management difficult (2). Numerous studies have sought to understand the pathogenesis of breast cancer, and to determine biomarkers for use as diagnostic and prognostic tools. A primary focus of research has been to investigate the role of microRNAs (miRNAs/miRs) in breast cancer (3). The first observation of miRNA deregulation in breast cancer was by Iorio et al (4), who performed microarray analysis to evaluate the miRNA expression profiles of 76 neoplastic breast tissue and 10 healthy adjacent tissue samples, and identified 29 disordered miRNAs, including miR-10b, miR-125b, miR-145, miR-21 and miR-155, which emerged as the most consistently deregulated in breast cancer. In order to elucidate the association between miRNAs and cancer metastasis, Farazi et al (5) conducted Solexa sequencing of small RNAs from 11 healthy breast tissue samples, 17 ductal carcinoma in situ samples, 151 invasive breast carcinoma samples and 6 cell lines; 269 novel miRNAs were identified and it was demonstrated that patients with increased expression of miR-423 were more likely to develop metastasis.

In addition to miRNAs, long non-coding RNAs (lncRNAs) have emerged as important factors contributing to the development and progression of breast cancer (6). lncRNAs are a heterogeneous group of non-coding RNAs, including the newly-discovered long intervening non-coding RNAs (lincRNAs), and they are defined as larger than 200 bp in length (7). Gupta et al (8) demonstrated that lincRNAs in the HOX loci become systematically dysregulated in breast cancer, and identified the lincRNA HOTAIR to be overexpressed in primary breast tumors and metastases; therefore, HOTAIR may serve as a predictor of eventual metastasis and mortality in primary mammary tumors.

Numerous studies have been performed on breast cancer; however, further research is required to elucidate the mechanisms involved and identify novel methods of treating breast cancer. The association between lncRNAs and miRNAs in human diseases has been previously studied, including some evidence to suggest that non-coding RNAs may act as competing endogenous RNAs (ceRNAs) (9,10). Wang et al (11) provided experimental evidence that non-coding RNAs may form an lncRNA-miRNA-mRNA interaction network to regulate liver cancer; it was demonstrated that the lncRNA HULC may function as an endogenous sponge, which interacts with and downregulates miRNA-372 and thereby decreases the translational repression of its target gene.

lthough a number of regulatory mechanisms influencing the association between gene expression and protein expression have been elucidated, the involvement of numerous lncRNAs and miRNAs in transcriptional regulation has not been investigated in breast cancer. In the present study, a bioinformatics approach was used to predict the regulatory mechanisms of miRNAs and lncRNAs, and to construct the lncRNA-miRNA-mRNA network in breast cancer. The results of the present study represent a view of breast cancer from a concurrent analysis of lncRNA, miRNA and mRNA

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