Table 1.
DEPs common to Jurkat and SUDHL5 after SAHA treatment, and their potential relevance to lymphomagenesis and/or response to HDACi treatment (fold changes are given in Fig. 1c)
| Gene symbol | Protein name | Potential relevance to lymphomagenesis and/or HDACi treatment |
|---|---|---|
| Common upregulated | ||
| MGST3 | Microsomal glutathione S-transferase 3 | Oxidant detoxification. Potentially upregulated as a response to HDAC-induced activation of Nrf2 |
| H1FX | Histone 1 FX | Elusive |
| HLA-A | HLA class I histocompatibility antigen, A-69 alpha chain | Several HLA class I alleles and variants have been associated with lymphoma development (reviewed in [86]) |
| EXOSC6 | Exosome complex component MTR3 | The RNA exosome has been implicated in both Ig CSR and SHM by targeting AID to transcribed dsDNA substrates and thus regulating its mutator activity [87] |
| NAXE | NAD(P)H-hydrate epimerase | NAXE (AI-BP) binds APOA1 and inhibits VEGFR2 signaling by promoting cholesterol efflux from caveolae/lipid rafts [88] |
| ANKRD13A | Ankyrin repeat domain-containing protein 13A | Part of the BCR signalosome. Promotes endocytosis of EGFR [89] |
| ANXA2 | Annexin A2 | ANXA2 promotes binding of lymphoma cells to epithelial cells [90] |
| TMEM205 | Transmembrane protein 205 | Increases resistance to cisplatin, potentially by exocytosis of platinum-containing vesicles [91] |
| Common downregulated | ||
| UNG* | Uracil-DNA glycosylase | Major DNA glycosylase for excision of genomic uracil. Deficiency associated with increased lymphoma risk in mice [92] |
| TYMS | Thymidylate synthase | Essential in de novo dTTP synthesis. Target of cancer antimetabolites. Decreased levels improves response to 5-fluorouracil [93] |
| UBE2C | Ubiquitin-conjugating enzyme E2 C | Correlated to tumor aggressiveness in a variety of lymphomas and its downregulation may contribute to the clinical efficacy of HDAC inhibitors in such malignancies [94] |
| LARP4 | La-related protein 4 | Tumor suppressor that may reduce metastatic potential [95] |
| UHRF1 | E3 ubiquitin-protein ligase UHRF1 | Reader of DNA and histone methylation that is essential to proliferation and is overexpressed in many cancers [96] |
| UBTF | Nucleolar transcription factor 1 | Transcription factor for ribosomal RNA. Depletion induces DNA damage and genomic instability [97] |
| CCDC86 | Coiled-coil domain-containing protein 86 | Cooperates with Myc to drive aggressive lymphoma growth. Knockdown sensitizes lymphoma B cells to Rituximab [98] |
| USP22 | Ubiquitin carboxyl-terminal hydrolase 22 | Histone deubiquitinase and component of the SAGA HAT complex [99]. Putative stem-cell marker in ALL [100] |
| RWDD4 | RWD domain-containing protein 4 | Downregulation suppresses proliferation and invasion in bladder cancer cells [101] |
| DDX56 | Probable ATP-dependent RNA helicase DDX56 | Oncogene in colorectal cancer and associated with lymphatic invasion and metastasis [102] |
| CDO1 | Cysteine dioxygenase type 1 | In CD4 + CTCL, CDO1 overexpression contributed to apoptosis-inhibition and chemoprotection [103] |
| RPL7L1 | 60S ribosomal protein L7-like 1 | Elusive |
* UNG was quantified by SILAC in Jurkat only, but nuclear isoform UNG2 found to be robustly downregulated in SUDHL5 by western analysis, targeted MS and IHC