Integration of microRNAome, proteomics and metabolomics to analyze arsenic-induced malignant cell transformation
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Youyou Zhou1,*, Yanfu Wang4,*, Juan Su1,*, Zheng Wu2, Chao Wang2, Weiming Zhong3, Xiaomei Liu2, Linhui Cui2, Xiaoyu Zhou2, Yufang Ma5, Yi Xin5, Jianglin Zhang1, Lisha Wu1, Xing Hu1, Xiang Chen1, Cong Peng1 and MingYang Gao2
1Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
2Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China
3Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
4Department of Gerontology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China
5Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044, Liaoning, China
*These authors have contributed equally to this work
Cong Peng, email: [email protected]
MingYang Gao, email: [email protected]
Keywords: arsenic, microRNAome, proteomics, metabolomics, cutaneous squamous cell carcinoma
Received: November 04, 2016 Accepted: April 21, 2017 Published: June 27, 2017
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.
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