Microarray expression profiling and co-expression network analysis
of circulating LncRNAs and mRNAs associated with neurotoxicity
induced by BPA
Received: 22 March 2017 /Accepted: 4 March 2018 / Published online: 18 March 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
A growing body of evidence has shown bisphenol A (BPA), an estrogen-like industrial chemical, has adverse effects on the
nervous system. In this study, we investigated the transcriptional behavior of long non-coding RNAs (lncRNAs) and mRNAs to
provide the information to explore neurotoxic effects induced by BPA. By microarray expression profiling, we discovered 151
differentially expressed lncRNAs and 794 differentially expressed mRNAs in the BPA intervention group compared with the
control group. Gene ontology analysis indicated the differentially expressed mRNAs were mainly involved in fundamental
metabolic processes and physiological and pathological conditions, such as development, synaptic transmission, homeostasis,
injury, and neuroinflammation responses. In the expression network of the BPA-induced group, a great number of nodes and
connections were found in comparison to the control-derived network. We identified lncRNAs that were aberrantly expressed in
the BPA group, among which, growth arrest specific 5 (GAS5) might participate in the BPA-induced neurotoxicity by regulating
Jun, RAS, and other pathways indirectly through these differentially expressed genes. This study provides the first investigation
of genome-wide lncRNA expression and correlation between lncRNA and mRNA expression in the BPA-induced neurotoxicity.
Our results suggest that the elevated expression of lncRNAs is a major biomarker in the neurotoxicity induced by BPA.
Keywords Bisphenol A
Long non-coding RNAs
The impacts of endocrine-disrupting compounds on human
health and the environment have drawn considerable attention
in recent years (Inadera 2015; Mustieles et al. 2015).
Bisphenol A (BPA), as the starting material in the production
of polycarbonates and epoxy resins, is one of the high produc-
tion volume (HPV) chemicals in the world (Suzuki et al.
2000). Humans may have been exposed to BPA in various
routes including water, air, soil environment, food contamina-
tion, surfaces, and plastic container. BPA exposure has recently
been demonstrated to be a risk factor for metabolic disorders
and can lead to adverse biological effects on nervous system.
To test whether BPA affected neurodevelopment, Yin et al.
examined the neural ectoderm specifically during differentia-
tion of mouse embryonic stem cells. The expression of four
neuroectoderm markers were significantly decreased in BPA
intervention samples compared to the controls (Yin et al.
2015). Wang and his colleges found that SH-SY5Y cell line
exposure to BPA interfered with protein formation related to
AD and led to AD-like neurotoxicity (Wang et al. 2017). These
results provided direct evidence of BPA-induced neurotoxicity.
Characterization of non-coding RNAs (ncRNAs) has
attracted increasing interests in recent years (Wapinski and
Wei Pang and Fu-Zhi Lian contributed equally to this work.
Responsible editor: Philippe Garrigues
* Zhi-xian Gao
* Yu-gang Jiang
Institute of Environmental and Operational Medicine, Da Li Dao,
Tianjin 300050, China
Department of Preventive Medicine, Hangzhou Normal University,
Hangzhou 310036, China
Tianjin Institute of Medical Equipment, Tianjin 300161, China
Environmental Science and Pollution Research (2018) 25:15006–15018