Table 1.
Top enriched pathways, and genes belonging to them, modulated by i6A and its three analogs in MCF7 human breast adenocarcinoma cells.
| Ingenuity canonical pathway | Nucleoside | P-valuea | B-H P-valueb | Ratioc | Genes |
|---|---|---|---|---|---|
| NRF2-mediated oxidative stress response (187 genes) | i6A | 2.63E−06 | 8.51E−04 | 0.086 | ATF4, DNAJA4, DNAJB1 (alias Hsp40), DNAJB6, DNAJB9, GCLC, GCLM, GPX2, HERPUD1, HMOX1 (alias HO-1), JUN, JUND, KEAP1, MAFG, PIK3R1, TXNRD1 (alias TRXR1) |
| allyl6A | 1.32E−05 | 4.57E−03 | 0.096 | ATF4, CREBBP, DNAJB6, DNAJB9, EIF2AK3, ENC1, GCLC, GCLM, GPX2, HERPUD1, HMOX1, JUN, JUND, MAFG, NFE2L2, PIK3CA, PIK3R1, TXNRD1 | |
| benzyl6A | 3.80E−05 | 1.32E−02 | 0.080 | ACTG2, ATF4, DNAJB1, DNAJB6, DNAJB9, GCLC, GCLM, HMOX1, JUN, JUNB, JUND, MAFG, PIK3CA, PIK3R1, TXNRD1 | |
| butyl6A | 2.75E−04 | 0.0832 | 0.075 | ATF4, CREBBP, DNAJB6, DNAJB9, ENC1, GCLC, GCLM, HERPUD1, HMOX1, JUN, JUND, MAFG, PIK3R1, TXNRD1 | |
| p53 signaling (95 genes) | i6A | 2.51E−04 | 0.0282 | 0.095 | GADD45A, GNL3, JUN, PIK3R1, PMAIP1, RPRM, SERPINB5, TNFRSF10B, TP53BP2 |
| allyl6A | 9.12E−03 | 0.223 | 0.084 | ADCK3, HIPK2, JUN, PIK3CA, PIK3R1, PMAIP1, RPRM, SIRT1 | |
| benzyl6A | 2.24E−03 | 0.130 | 0.084 | ADCK3, APAF1, GADD45A, JUN, PIK3CA, PIK3R1, PMAIP1, RPRM | |
| butyl6A | 3.72E−02 | 0.402 | 0.063 | GADD45A, JUN, PIK3R1, PMAIP1, RPRM, SIRT1 | |
| Glucocorticoid receptor signaling (277 genes) | i6A | 2.63E−04 | 0.0282 | 0.058 | ANXA1, CDK7, CEBPB, CREB1, CREBZF, DUSP1, GTF2B, HSPA1A/HSPA1B, HSPA1L, HSPA4, HSPA6, JUN, NFKBIE, PIK3R1, PLAU, SOS1 |
| allyl6A | 2.14E−04 | 0.0372 | 0.072 | ANXA1, CEBPB, CREB1, CREBBP, DUSP1, FOXO3, GTF2B, HSPA1A/HSPA1B, HSPA4, JUN, NFAT5, NRIP1, PIK3CA, PIK3R1, PLAU, SMAD4, TAF4, TAF5, TAF6L, TRAF6 | |
| benzyl6A | 7.94E−04 | 0.0741 | 0.058 | CREB1, CREBZF, DUSP1, FOXO3, GTF2B, GTF2H1, HSPA1A/HSPA1B, HSPA4, HSPA6, JUN, NFAT5, NRIP1, PIK3CA, PIK3R1, TAF10, TAF5 | |
| butyl6A | 5.50E−04 | 0.0832 | 0.061 | ANXA1, CDK7, CEBPB, CREB1, CREBBP, CREBZF, DUSP1, GTF2B, HSPA1A/HSPA1B, HSPA4, JUN, NRIP1, PIK3R1, PLAU, TAF4B, TAF5, TRAF6 | |
a
Right-tailed Fisher’s exact test run in Ingenuity Pathway Analysis software.
b
Multiple testing correction with the Benjamini–Hochberg method run in Ingenuity Pathway Analysis software.
c
Ratio between the number of genes in the dataset (i.e. genes whose expression level changed by ≥1.5 fold and at P < 1.0 × 10−4) that map to the pathway and the total number of genes in the pathway.
In bold are the down-regulated genes.