Integration of microRNAome, proteomics and metabolomics to analyze arsenic-induced malignant cell transformation

Abstract

// Youyou Zhou 1, * , Yanfu Wang 4, * , Juan Su 1, * , Zheng Wu 2 , Chao Wang 2 , Weiming Zhong 3 , Xiaomei Liu 2 , Linhui Cui 2 , Xiaoyu Zhou 2 , Yufang Ma 5 , Yi Xin 5 , Jianglin Zhang 1 , Lisha Wu 1 , Xing Hu 1 , Xiang Chen 1 , Cong Peng 1 and MingYang Gao 2 1 Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China 2 Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China 3 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China 4 Department of Gerontology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China 5 Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044, Liaoning, China * These authors have contributed equally to this work Correspondence to: Cong Peng, email: pengcongxy@csu.edu.cn MingYang Gao, email: dlgaomingyang@126.com Keywords: arsenic, microRNAome, proteomics, metabolomics, cutaneous squamous cell carcinoma Received: November 04, 2016      Accepted: April 21, 2017      Published: June 27, 2017 ABSTRACT Long-term exposure to arsenic has been linked to tumorigenesis in different organs and tissues, such as skin; however, the detailed mechanism remains unclear. In this present study, we integrated “omics” including microRNAome, proteomics and metabolomics to investigate the potential molecular mechanisms. Compared with non-malignant human keratinocytes (HaCaT), twenty-six miRNAs were significantly altered in arsenic-induced transformed cells. Among these miRNAs, the differential expression of six miRNAs was confirmed using Q-RT-PCR, representing potential oxidative stress genes. Two-dimensional gel electrophoresis (2D-PAGE) and mass spectrometry (MS) were performed to identify the differential expression of proteins in arsenic-induced transformed cells, and twelve proteins were significantly changed. Several proteins were associated with oxidative stress and carcinogenesis including heat shock protein beta-1 (HSPB1), peroxiredoxin-2 (PRDX2). Using ultra-performance liquid chromatography and Q-TOF mass spectrometry (UPLC/Q-TOF MS), 68 metabolites including glutathione, fumaric acid, citric acid, phenylalanine, and tyrosine, related to redox metabolism, glutathione metabolism, citrate cycle, met cycle, phenylalanine and tyrosine metabolism were identified and quantified. Taken together, these results indicated that arsenic-induced transformed cells exhibit alterations in miRNA, protein and metabolite profiles providing novel insights into arsenic-induced cell malignant transformation and identifying early potential biomarkers for cutaneous squamous cell carcinoma induced by arsenic.