AMPD3 is associated with the malignant characteristics of gastrointestinal stromal tumors

Abstract

Abstract. Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. It is well known that activating mutations in the receptor tyrosine kinases KIT and platelet-derived growth factor receptor-α have essential roles in the pathogenesis of GISTs. The activation of these receptor protein kinases triggers multiple signaling pathways that promote cell proliferation and survival; however, the exact mechanism by which the activation of these kinases promotes the progression of GISTs remains uncertain. The aim of the present was to search for genes that are associated with the progression of GIST. The present study used reverse transcription-quantitative polymerase chain reaction to demonstrate that adenosine monophosphate deaminase 3 (AMPD3) was highly expressed in GISTs. Furthermore, transfection of GIST-T1 cells with KIT-specific small interfering RNA (siRNA) demonstrated that the expression of AMPD3 was dependent on KIT expression, while the depletion of AMPD3 in human GIST-T1 cells using AMPD3-specific siRNA resulted in the suppression of cell migration and invasion. In addition, AMPD3 depletion sensitized GIST-T1 cells to the tyrosine kinase inhibitor imatinib. The results of the present suggested that the combined inhibition of tyrosine kinases and AMPD3 may be effective for the treatment of GISTs.

Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus

“…In our research, the elevated Slc22a5 in the hippocampus of GF mice suggests that carnitine transport and/or energy production may be increased, and thus may play a protective role. Furthermore, adenosine monophosphate deaminase 3 (Ampd3) is a key enzyme in the catabolic pathway of adenylate that breaks adenosine monophosphate into inosine monophosphate, and eventually produces uric acid 49 , 50 . Ampd3 is ubiquitously expressed; it can regulate the energy metabolism of the body and may regulate the energy balance 50 .…”

“…Furthermore, adenosine monophosphate deaminase 3 (Ampd3) is a key enzyme in the catabolic pathway of adenylate that breaks adenosine monophosphate into inosine monophosphate, and eventually produces uric acid 49 , 50 . Ampd3 is ubiquitously expressed; it can regulate the energy metabolism of the body and may regulate the energy balance 50 . ATP mediates lipid and protein synthesis, buffers intracellular calcium, and regulates apoptosis and resilience pathways 51 .…”

Maternal Choline Supplementation during Normal Murine Pregnancy Alters the Placental Epigenome: Results of an Exploratory Study

“…Tfpi2 (tissue factor pathway inhibitor 2) inhibits the activity of matrix metalloproteinases and regulates placental perfusion [ 40 , 41 ], while deficiency of Aqp1 (aquaporin 1) causes aberrant placental vascularization and fetal overgrowth [ 37 ]. Although the consequences of altered expression of Ampd3 (AMP deaminase 3), a known regulator of fetal muscle and liver development [ 42 ], in the placenta remain to be examined, Ampd3 deficiency in cancer cells has been shown to inhibit cell proliferation and invasion [ 43 ]. Collectively, the choline-induced upregulation of all these placental imprinted genes would be expected to improve placental vascularization and perfusion, likely contributing to the choline-induced beneficial effects on placental transport efficiency and fetal development reported previously [ 17 ].…”

Biomarkers Associated with Tumor Heterogeneity in Prostate Cancer

“…Overexpression of Neuropilin and tolloid-like 2 ( NETO2 ) has been found in many cancer types including proliferating hemangiomas and colorectal carcinoma [24] , [25] , [26] and thus could be considered as a potential biomarker in tumor progression. Recent study have suggested that adenosine monophosphate deaminase 3 ( AMPD3 ) deletion suppresses the proliferation, migration, and invasion of gastrointestinal stromal tumor [27] . AMPD3 expression is positively correlated with ERG overexpression and PTEN inactivation in prostate cancer [28] , [29] .…”