Concerted changes in transcriptional regulation of genes involved in DNA methylation, demethylation, and folate-mediated one-carbon metabolism pathways in the NCI-60 cancer cell line panel in response to cancer drug treatment

Krushkal, Julia; Zhao, Yingdong; Hose, Curtis; Monks, Anne; Doroshow, James H.; Simon, Richard

doi:10.1186/s13148-016-0240-3

Table 1 Summary of time-specific drug treatment effects on gene expression in the NCI-60 cell lines

From: Concerted changes in transcriptional regulation of genes involved in DNA methylation, demethylation, and folate-mediated one-carbon metabolism pathways in the NCI-60 cancer cell line panel in response to cancer drug treatment

Gene	5-Azacytidine	Doxorubicin	Vorinostat	Paclitaxel	Cisplatin
DNMT1	H↓24^a; L↓24	H↓6, 24^a	HL↓2; H↓6^a,24^b; L↓6,24^a	H↓24	NC
DNMT3A	NC	NC	H↓6^a,24^a; L↓6	NC	NC
DNMT3B	NC	H↓6^a, 24^a	H↑2^a,6^b; L↑2,6^a	NC	NC
DNMT3L	NC	NC	NC	NC	NC
TET3	H↑24^a	NC	L↓6^a; HL↓24^a	NC	NC
AICDA	NC	NC	NC	NC	NC
APOBEC1	NC	NC	NC	NC	NC
APOBEC2	NC	NC	NC	NC	NC
APOBEC3A	NC	NC	NC	NC	NC
APOBEC3C	H↓24^a	L↑24^a	H↓6^a; HL↓24^a	NC	H↑24^a
TDG	H↑6,24^a	NC	H↓2,6,24^a; ↓6,24	H↑24	H↑24
GADD45A	H↑2^b; HL↑6^a,24^b	H↑24^c; L↑24^b	H↑24^b; L↑24^a	HL↑24^b	H↑6^a,24^bd; L↑24^ad
IDH1	NC	H↑2,6; L↓24^b	H↑2^a,6^a,24^a; L↑2,6^a,24^a	L↓6; HL↓24^a	H↓24^a
IDH2	H↓24^a	H↑6,24^a; L↑24	NC	HL↓24	L↑24
MGMT	H↓24^a; L↓24	H↓24^a	NC	NC	H↓24^b
MBD1	H↑24^a; L↑24	H↑6,24^a; L↑24	H↑6^a,24^a	HL↑24	H↑24^ad
MBD2	H↓24	HL↓24	H↓24	NC	NC
MBD3	NC	NC	HL↓6^a,24^a	NC	NC
MBD4	H↓2^aHL↑6	HL↑2; H↑6,24^a	HL↑2,6^a	NC	H↑6,24^a; L↑24
MeCP2	NC	H↓6,24	HL↓6^a; H↓24^a; L↓24;	NC	NC
PCNA	L↑6; HL↓24^a	H↑2,6^a; L↑6,24^a	L↓6; HL↓24^a	HL↓24	H↑6,24
USP7	HL↓6; H↑24	HL↓6,24^a	H↓2,6^a,24^a; L↓6	NC	H↓24
SMUG1	H↓2; HL↓6; H↑24^a; L↑24	H↑24^a; L↑24^d	HL↑24^a	NC	NC
MTHFR	NC	NC	NC	NC	NC
MTHFD1	H↓24^a; L↓24	H↓24^b	H↓6^a,24^a; L↓24	HL↓24	NC^d
MTR	NC	HL↓6; H↓24^a	H↓6^a,24^a; L↓6	H↓24^a; L↓24	H↓6,24^ad
MTRR	H↑6^a,24^a	L↓24^a	H↑6^a; L↓24	NC	H↑6
CBS	H↑24^b; L↑24^a	NC	NC	HL↓24^a	NC
TCN2	NC	NC	H↑24^b	NC	NC
SHMT1	H↓24^a	H↓24^a	HL↓24	HL↓24	NC
TYMS	H↓24^a; L↓24	H↑2,6^a; L↑6	HL↓2; H↓6^b,24^b; L↓6^a,24^a	HL↓24	H↑24
DHFR	H↓24^b; L↓24^a	H↑2, 24^a; HL↑6	HL↓24^b	HL↓24	H↑6; L↑24
BHMT	NC	H↑24	NC	NC	NC
CTH	H↑6^b; L↑6^a; HL↑24^b	H↑6^a,24^b	H↑2^a,6^b,24^b; L↑6^a,24^a	NC	H↑6,24^bd
AHCY	H↓24^a; L↓24	HL↑6; L↑24	H↓24^a; L↓2,6,24	HL↓24	H↑6
ALDH1L1	NC	NC	NC	NC	NC
ATIC	H↓6; HL↑24	H↓24^a; L↓24	H↓6^a,24^a; L↓2,6,24	NC	NC
GART	HL↑24	H↓6^a,24^a; L↓24	H↓6^a,24^a; L↓6,24	HL↓24^d	NC
MTHFS	NC	H↓24^a	H↓2; HL↓6^a; H↓24^b; L↓24^b	NC	NC
FTCD	H↓24	NC	H↑24^c	NC	NC
MAT1A	NC	NC	NC	NC	NC
MAT2A	H↓6,24^a	H↓6^a,24^b; L↓6,24	NC	NC	H↓24^a
MAT2B	H↓24; L↓2	NC	H↑2^a; L↑2; HL↑6	NC	NC
NNMT	NC	NC	H↓2^c,6^b; L↓2,6^a	NC	NC
PON1	NC	NC	NC	NC	NC
SLC19A1	HL↓24	H↓6^a; HL↓24^a	H↓6^a; L↓6; HL↓24^a	L↓24	H↓24
FOLR1	NC	NC	H↑24^b	NC	NC
FOLR2	NC	H↑24^ad	NC	NC	NC
FOLR3	NC	NC	NC	NC	NC
SHMT2	H↑6; HL↑24^a	H↑6; H↓24^a	H↓24^a; L↓24	HL↓24	H↑6
AMT	H↓6	HL↑24	H↑24^a	NC	NC
MTHFD2	H↑6^a; L↑6; HL↑24^a	NC	HL↓24^a	L↓24^a	H↑6,24^a
MTHFD2L	NC	H↓6^a,24^b; L↓24^a	NC	NC	H↓24^a; L↑2
PEMT	NC	HL↓24^a	HL↓6^a,24^a	NC	H↓24^a; L↓24
FOLH1	H↓24^a	NC	NC	NC	NC
ALDH2	NC	H↑6; HL↑24^a	HL↑6^a; H↑24^a	NC	NC

Information about gene roles is provided in Additional file 1: Table S1. Concerted changes in expression (↑, upregulated or ↓, downregulated) are shown for microarray experiments in which nearly all cell lines had a change in the same direction, with no more than 15 cell lines showing a change in the opposite direction. Expression changes are shown if observed for the high concentration only (H), low concentration only (L), or both high and low concentrations (HL) of each antitumor agent. The time when the change was observed is also indicated. The drug concentrations for each agent are listed in the “Methods”. NC (not concerted), indicates that either the criteria of concerted expression were not satisfied or that those criteria were not indicative of concerted expression due to a large amount of missing data for a specific gene in a given microarray experiment. For example, H↑2,6^a; HL↓24 indicates that a gene was upregulated after treatment with the high concentration of the drug at 2 and 6 h after treatment, with the change of log₂ expression values at 6 h in at least some cell lines being ≥1 or ≤−1, and that the same gene was downregulated at both high and low concentrations of the drug at 24 h after treatment
^aConcerted expression change as described above and log₂ FC (the difference of log₂ expression values between treated and untreated cells) in that direction in some cell lines was ≥1 or ≤−1
^bConcerted expression change and log₂ FC in that direction in some cell lines was ≥2.5 or ≤−2.5
^cConcerted expression change as described above and log₂ FC in that direction in some cell lines was ≥4 or ≤−4
^dFor at least one drug concentration and at least one time point, changes in expression were significantly correlated with log(GI50) as shown in Table 2

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ISSN: 1868-7083

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