Contents lists available at ScienceDirect Experimental and Molecular Pathology journal homepage: www.elsevier.com/locate/yexmp Expression analysis of vimentin and the related lncRNA network in breast cancer Mehdi Mohebi a , Soudeh Ghafouri-Fard a, ⁎ , Mohammad Hossein Modarressi b , Sepideh Dashti a , Ali Zekri c , Vahid Kholghi-Oskooei d,e , Mohammad Taheri f, ⁎ a Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran b Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran c Department of Medical Genetics and Molecular biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran d Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran e Health Sciences Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran f Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran ARTICLE INFO Keywords: VIM VIM-AS1 AGAP2 AGAP2-AS1 Breast cancer ABSTRACT Vimentin (VIM) is a mesenchymal marker which is expressed in some cancer types including breast cancer. A long non-coding RNA (lncRNA) has been identified to be transcribed from VIM gene locus and positively regulate expression of VIM. This lncRNA has been named as VIM-antisense 1 (VIM-AS1). Expression of VIM is also regulated by another lncRNA namely AGAP2-antisense RNA 1 (AGAP2-AS1). In the current study, we aimed at identification of the expression pattern of VIM, VIM-AS1, AGAP2 and AGAP2-AS1 in 78 breast cancer samples and their paired adjacent non-cancerous tissues (ANCTs) by means of real time PCR. All mentioned genes were significantly down-regulated in tumoral tissues compared with ANCTs (P values less than 0.000). Relative ex- pression of VIM-AS1 in tumoral tissues versus ANCTs was associated with menopause age (P = .02) in a way that this gene was down-regulated in most of patients whose menopause age was between 40 and 50 years. Moreover, AGAP2–AS1 relative expression was associated with patients' body mass index (P = .03). There were trends toward association between VIM relative expression and tumor size (P = .07) and association between VIM-AS1 relative expression and obesity (P = .06). Expression of VIM was significantly higher in tumoral tissues of patients who had history of hormone replacement therapy compared with those without such history (P = .03). Moreover, expression levels of both VIM and AGAP2-AS1 were lower in patients whose menarche age was between 10 and 12 years old compared with those whose menarche age was between 13 and 15 years old (P values = .01 and 0.04, respectively). Transcript quantities of VIM, VIM-AS1, AGAP2 and AGAP2-AS1 were correlated with each other both in tumoral tissues and in ANCTs. Among four assessed genes, AGAP2 had the best diagnostic power for discrimination of tumoral tissues from ANCTs (AUC value = 0.87). Combination of four genes led to enhancement of AUC value to 0.94. The current study shows the importance of VIM and its associated lncRNAs in breast cancer and potentiates these genes as biomarkers for this malignancy. Moreover, these lncRNAs might be regarded as therapeutic targets in breast cancer. 1. Introduction Breast cancer is the most frequently diagnosed cancer and the most important cause of cancer mortality among women accounting for more than 2 million new cases of cancer and more than 600,000 cases of cancer-related deaths worldwide (Bray et al., 2018). There are a number of known risk factors for development of breast cancer among them are early menarche age, late menopause age, nulliparity, oral contraceptive (OCP) intake, hormone replacement therapy (HRT) and obesity (Cancer Epidemiology and Prevention, 2018). As a hetero- geneous disease, breast cancer is associated with abnormal regulation of numerous signaling pathways including Notch, Wnt/β-catenin, TGF- β, and MAPK pathways (Abolghasemi et al., 2020b).Notably, each of these pathways are regulated by a number of epigenetic factors such as miRNAs (Abolghasemi et al., 2020a). Studies aimed at identification of underlying mechanisms of breast cancer development have shown aberrant expression of several genes and pathways. A well-known me- chanism for invasiveness of breast cancer cells is epithelial- https://doi.org/10.1016/j.yexmp.2020.104439 Received 19 March 2020; Received in revised form 5 April 2020; Accepted 10 April 2020 ⁎ Corresponding authors. E-mail addresses: s.ghafourifard@sbmu.ac.ir (S. Ghafouri-Fard), mohammad_823@yahoo.com (M. Taheri). Experimental and Molecular Pathology 115 (2020) 104439 Available online 10 April 2020 0014-4800/ © 2020 Published by Elsevier Inc. T