Targeting the nucleotide metabolism proteins of the NUDIX family and SAMHD1 in cancer

Abstract

: The nucleotide metabolism has been targeted for many years and in various clinical settings, including cancer. The increased knowledge of certain enzymes involved in this metabolism and in associated cellular processes accumulated over the last few years, gives important information to the druggability of certain proteins and to the use of inhibitors for others. Here, we review recent data on such enzymes with major interest in drug development, i.e. SAMHD1 and the proteins of the NUDIX family. These include information on their roles in cancer progression, correlations with clinical outcome in cancer patients, and development and study of enzymatic inhibitors.

Transcriptomic and Functional Evidence That miRNA193a-3p Inhibits Lymphatic Endothelial Cell (LEC) and LEC + MCF-7 Spheroid Growth Directly and by Altering MCF-7 Secretome

“…On one side they directly promote antitumor response by suppressing tumor growth and on the other side they induce tumor progression by establishing progrowth conditions in the tumor microenvironment [67,68]. The DRGs of IFN α/β signaling and cellular response to type I IFN, which were downregulated, include genes involved in tumor progression (SAMHD1 [69], PLSCR1 [70], IFITs (IFIT1, IFIT2, and IFIT3 [71]), TAPs (TAP1 and TAP2) [72], cell proliferation, apoptosis/cell survival, metastasis, angiogenesis (PSMB8 [73], PSMB9 [74], IFI6 [75], and IFI27 [76]), OAS's (OAS1, OAS2, and OAS3) [77], IFITMs (IFITM1, IFITM2, and IFITM3) [78,79], UBE2L6 [80], USP18 [81], tumorigenesis and genes with a role in cancer STAT1 [82], RSAD2 [83], IFI6 [84], and HLAs-class-I (HLA-A, HLA-B, HLA-C, HLA-F, and HLA-G) [85]). The upregulated genes (by ≥ 1.5-fold) involved in apoptosis and autophagy, cell death, and cell growth inhibition were S100A8 and S100A9 [86], MMP1 [87], MMP13 [88], AREG [89], PLIN2 [90], and AKR1C1 [91].…”

Micro-RNA193a-3p Inhibits Breast Cancer Cell Driven Growth of Vascular Endothelial Cells by Altering Secretome and Inhibiting Mitogenesis: Transcriptomic and Functional Evidence

“…Type I interferon, including IFN-α and IFN-β, has contradictory effects; it directly promotes antitumor response, suppressing tumor growth and induces tumor progression by establishing conditions in the tumor microenvironment that facilitate tumor growth [48,49]. The DRGs of interferon alpha/beta signaling and cellular response to type I interferon that were downregulated include genes involved in tumor progression (CCL20 [50], SAMHD1 [51], TRIM 22 [52], PLSCR1 [53], IFITs (IFIT1, IFIT2, IFIT3, IFIT5) [54], PML [55], PSMF1 [56], TAPs (TAP1, TAP2) [57], LGALS9 [58], MX1 [59]), cell proliferation, metastasis, angiogenesis (TRIM 38 [60], MX2 [61], PSMA3 [62], PSMB8 [63], PSMB9 [64], CXCL10 [65], IFI27 [66], IRF9 [67], OASs (OAS1, OAS2, OAS3) [68], IFITMs (IFITM1, IFITM2, IFITM3) [69], UBE2L6 [70], USP18 [71]), tumorigenesis, and genes that play roles in cancer (STAT1 [72], TRIM38 [60], NUP38 [73], RSAD2 [74], IFI6 [75], HLAs (HLA-A, HLA-B, HLA-C, HLA-F) [76], XAF 1 [77], ADAR [78]). The up-regulated genes were involved in apoptosis, cell-death, cell growth inhibition (PID1 [79], TRIM31 [80], CCL23 [81], CCR7 [82], EIF4A2 [83], GAS6-AS1 [84], UBE1L (UBA7) [85]).…”