TY - JOUR
T1 - Delineating the Effects of Passaging and Exposure in a Longitudinal Study of Arsenic-Induced Squamous Cell Carcinoma in a HaCaT Cell Line Model
AU - Banerjee, Mayukh
AU - Al-Eryani, Laila
AU - Srivastava, Sudhir
AU - Rai, Shesh N.
AU - Pan, Jianmin
AU - Kalbfleisch, Theodore S.
AU - States, J. Christopher
N1 - Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Cutaneous squamous cell carcinoma (cSCC) is a major deleterious health effect of chronic arsenic (iAs) exposure. The molecular mechanism of arsenic-induced cSCC remains poorly understood. We recently demonstrated that chronic iAs exposure leads to temporally regulated genome-wide changes in profiles of differentially expressed mRNAs and miRNAs at each stage of carcinogenesis (7, 19, and 28 weeks) employing a well-established passage-matched HaCaT cell line model of arsenic-induced cSCC. Here, we performed longitudinal differential expression analysis (miRNA and mRNA) between the different time points (7 vs 19 weeks and 19 vs 28 weeks) within unexposed and exposed groups, coupled to expression pairing and pathway analyses to differentiate the relative effects of long-term passaging and chronic iAs exposure. Data showed that 66-105 miRNA [p <. 05; log2(fold change) > I1I] and 2826-4079 mRNA [p <. 001; log2(fold change) > I1I] molecules were differentially expressed depending on the longitudinal comparison. Several mRNA molecules differentially expressed as a function of time, independent of iAs exposure were being targeted by miRNA molecules which were also differentially expressed in a time-dependent manner. Distinct pathways were predicted to be modulated as a function of time or iAs exposure. Some pathways were also modulated both by time and exposure. Thus, the HaCaT model can distinguish between the effects of passaging and chronic iAs exposure individually and corroborate our previously published data on effects of iAs exposure compared with unexposed passage matched HaCaT cells. In addition, this work provides a template for cell line-based longitudinal chronic exposure studies to follow for optimal efficacy.
AB - Cutaneous squamous cell carcinoma (cSCC) is a major deleterious health effect of chronic arsenic (iAs) exposure. The molecular mechanism of arsenic-induced cSCC remains poorly understood. We recently demonstrated that chronic iAs exposure leads to temporally regulated genome-wide changes in profiles of differentially expressed mRNAs and miRNAs at each stage of carcinogenesis (7, 19, and 28 weeks) employing a well-established passage-matched HaCaT cell line model of arsenic-induced cSCC. Here, we performed longitudinal differential expression analysis (miRNA and mRNA) between the different time points (7 vs 19 weeks and 19 vs 28 weeks) within unexposed and exposed groups, coupled to expression pairing and pathway analyses to differentiate the relative effects of long-term passaging and chronic iAs exposure. Data showed that 66-105 miRNA [p <. 05; log2(fold change) > I1I] and 2826-4079 mRNA [p <. 001; log2(fold change) > I1I] molecules were differentially expressed depending on the longitudinal comparison. Several mRNA molecules differentially expressed as a function of time, independent of iAs exposure were being targeted by miRNA molecules which were also differentially expressed in a time-dependent manner. Distinct pathways were predicted to be modulated as a function of time or iAs exposure. Some pathways were also modulated both by time and exposure. Thus, the HaCaT model can distinguish between the effects of passaging and chronic iAs exposure individually and corroborate our previously published data on effects of iAs exposure compared with unexposed passage matched HaCaT cells. In addition, this work provides a template for cell line-based longitudinal chronic exposure studies to follow for optimal efficacy.
KW - HaCaT
KW - RNA-seq
KW - arsenic
KW - passage matching
KW - pathway analysis
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U2 - 10.1093/toxsci/kfab129
DO - 10.1093/toxsci/kfab129
M3 - Article
C2 - 34730829
AN - SCOPUS:85123901489
SN - 1096-6080
VL - 185
SP - 184
EP - 196
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 2
ER -