PTP4A3, A Novel Target Gene of HIF-1alpha, Participates in Benzene-Induced Cell Proliferation Inhibition and Apoptosis through PI3K/AKT Pathway

Abstract

Benzene, a commonly used chemical, has been confirmed to specifically affect the hematopoietic system as well as overall human health. PTP4A3 is overexpressed in leukemia cells and is related to cell proliferation. We previously found that HIF-1alpha was involved in benzene toxicity and PTP4A3 may be the target gene of HIF-1alpha via ChIP-seq. The aim of this study is to confirm the relationship between HIF-1alpha and PTP4A3 in benzene toxicity, as well as the function of PTP4A3 on cell toxicity induced by 1,4-benzoquinone (1,4-BQ). Our results indicate that HIF-1alpha could regulate PTP4A3 with in vivo and in vitro experiments. A cell line with suppressed PTP4A3 was established to investigate the function of PTP4A3 in 1,4-BQ toxicity in vitro. The results revealed that cell proliferation inhibition was more aggravated in PTP4A3 low-expression cells than in the control cells after 1,4-BQ treatment. The relative oxygen species (ROS) significantly increased in cells with inhibited PTP4A3, while the rise was inferior to the control cells at the 20 μM 1,4-BQ group. An increase in DNA damage was seen in PTP4A3 down-regulated cells at the 10 μM 1,4-BQ group, whereas the results reversed at the concentration of 20 μM. Moreover, the apoptosis rate increased higher in down-regulated PTP4A3 cells after 1,4-BQ exposure. In addition, PI3K/AKT pathway was significantly restrained in cells with inhibited PTP4A3 after 1,4-BQ treatment. Our results indicate that HIF-1alpha may regulate PTP4A3 to be involved in benzene toxicity. Inhibition of PTP4A3 could aggravate cell proliferation suppression and apoptosis by regulating PI3K/AKT pathway after 1,4-BQ treatment.

Effect of mir‐92a‐3p on hydroquinone induced changes in human lymphoblastoid cell cycle and apoptosis

“…[22][23][24] It has been reported in the literature that activation of the PI3K/AKT signaling pathway is involved in benzoquinone-induced cell proliferation and apoptosis, and inhibition of oxidative stress-mediated apoptosis to prevent benzeneinduced haemocytopenia. 25,26 Here we demonstrate a role for the miR-92a-3p/TOB1 axis in the HQ-induced malignant transformation of TK6 cells, providing a reference or basis for studies to intervene in benzene toxicity and prevent treatment.…”

“…It has been found that inhibition of the PI3K/AKT pathway can act as a pro‐survival factor in leukemia stem cells and early leukemia in all types of leukemia and it is considered a new therapeutic approach 22–24 . It has been reported in the literature that activation of the PI3K/AKT signaling pathway is involved in benzoquinone‐induced cell proliferation and apoptosis, and inhibition of oxidative stress‐mediated apoptosis to prevent benzene‐induced haemocytopenia 25,26 …”

PTP4A3 Is a Prognostic Biomarker Correlated With Immune Infiltrates in Papillary Renal Cell Carcinoma

“…PTP4A3 is a dual phosphatase and is known to act on ezrin, cytokeratin and integrin β1 ( 46 – 48 ). PTP4A3 is involved in the regulation of cell proliferation, migration and invasion through the PI3K-AKT-ERK pathway and destabilizes telomeres through the NFкB-RAP1-TRF2 axis ( 18 , 23 , 24 , 49 ). Moreover, PTP4A3 contributes to the secretion of inflammatory factors, which recruit more immune cells to the tumor microenvironment.…”

Protein Tyrosine Phosphatase PRL-3: A Key Player in Cancer Signaling

“…Compared with non-MDR cancer and normal cells, the levels of ROS and the activity of clearance/antioxidant enzymes are usually increased in drug-resistant cancer cells [ 130 ]. Several studies have indicated that PRL-3 decreases intracellular ROS levels and induces overexpression of glycolysis enzymes and molecules, contributing to enhanced tumor cell proliferation and invasion [ 131 , 132 , 133 ]. Silencing PRL-3 in colon cancer cells has been shown to lead to a ROS-dependent DNA damage response and senescence, indicating a potential link between PRL-3 and acquired resistance [ 121 ].…”