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Table 5 Literature supporting the yeast phenomic doxorubicin model

From: A yeast phenomic model for the influence of Warburg metabolism on genetic buffering of doxorubicin

y/hGene Process PharmacoDB Description Ref Doxorubicin relevance/validation
Enhancement/UES
MUS81/MUS81 Topological change MUS81 MUS81 structure-specific endonuclease subunit [103, 181, 182] Knockdown (shRNA) increases cisplatin and epirubicin (doxorubicin analog)-induced apoptosis of HCC cells.
SOD1/SOD1/CCS Oxidative stress: complexes III and IV; protein import into mito matrix SOD1; CCS Superoxide dismutase [8, 11, 72,73,74] Doxorubicin causes depletion of cardiolipin and cytochrome c in cardiomyocytes, which reduces workload capacity and accelerates aging; TIM/TOM deficiency induces oxidative stress, oxidative stress enhances doxorubicin toxicity.
CDC8/DTYMK; CDC21/TYMS dTTP biosynthetic process NA Thymidylate kinase; thymidylate synthetase [127] shRNA silencing of DTYMK enhances doxorubicin in cancer cell lines.
HDA1/HDAC6 Histone deacetylation HDAC6 Histone deacetylase 6 [235, 236] shRNA inhibition of HDAC6 enhances doxorubicin treatment; HDAC6 inhibition reduces cardiomyocyte toxicity.
Suppression/OES
VPS53/VPS53 Sphingolipid homeostasis VPS53 GARP complex subunit [204] Transfection with VPS53 transcript induces apoptosis and sensitizes cervical cancer cells to doxorubicin.
ELO2/3/ELOVL6 Fatty acid elongase activity; ceramide/phytosphingosine ELOVL6 ELOVL fatty acid elongase 6; doxorubicin induces ceramide overproduction contributing to doxorubicin induced apoptosis [12, 13, 150,151,152,153,154,155,156] Loss of genes involved in sphingolipid/ceramide metabolism suppress doxorubicin cytotoxicity in our experiment; treatment with by N,N-dimethyl phytosphingosine sensitizes leukemia cells to doxorubicin.
POB3/SSRP1 FACT complex SSRP1 Structure-specific recognition protein 1 [20] FACT complex binds and “traps” disassembled chromatin in response to doxorubicin induced nucleosome disassembly, which induces chromatin damage.
ARP2/ACTR2 Actin cortical patch localization; APR2/3 complex ACTR2 ARP2 actin-related protein 2 homolog [158,159,160,161,162, 188] ROCK1 deletion enhances doxorubicin resistance in fibroblasts by altering the actin cytoskeleton and protecting from apoptosis.