DDIT3 (DNA Damage-inducible transcript 3),也称为CHOP (C/EBP Homologous Protein)是一种属于CCAAT/增强子结合蛋白家族的转录因子。DDIT3是肿瘤细胞中响应内质网应激和DNA损伤的关键分子。近年来,DDIT3在恶性肿瘤中的研究取得了显...DDIT3 (DNA Damage-inducible transcript 3),也称为CHOP (C/EBP Homologous Protein)是一种属于CCAAT/增强子结合蛋白家族的转录因子。DDIT3是肿瘤细胞中响应内质网应激和DNA损伤的关键分子。近年来,DDIT3在恶性肿瘤中的研究取得了显著进展,其在多种肿瘤的发生发展中扮演着重要角色。本综述旨在总结DDIT3在恶性肿瘤中的研究进展,探讨DDIT3的异常表达与多肿瘤恶性进展的相关性,以及作为潜在治疗靶点的可能性,为针对肿瘤的深入研究和治疗提供理论依据。DNA Damage-inducible transcript 3 (DDIT3), also known as C/EBP Homologous Protein (CHOP), is a transcription factor belonging to the CCAAT/enhancer-binding protein family. It plays a pivotal role in the cellular stress response pathways, responding to endoplasmic reticulum stress and DNA damage in tumor cells. Recent years have seen significant progress in the study of DDIT3 in malignant tumors, where it plays an important role in the occurrence and development of various cancers. This review aims to summarize the research progress of DDIT3 in malignant tumors, explore the correlation between the abnormal expression of DDIT3 and the malignant progression of multiple tumors, and discuss its potential as a therapeutic target, providing a theoretical basis for in-depth research and treatment of cancer.展开更多
Tris(1,3-dichloro-2-propyl) phosphate(TDCIPP) is a commonly used organophosphatebased flame retardant and can bio-accumulate in human tissues and organs. As its structure is similar to that of neurotoxic organophospha...Tris(1,3-dichloro-2-propyl) phosphate(TDCIPP) is a commonly used organophosphatebased flame retardant and can bio-accumulate in human tissues and organs. As its structure is similar to that of neurotoxic organophosphate pesticides, the neurotoxicity of TDCIPP has raised widespread concerns. TDCIPP can increase neuronal apoptosis and induce autophagy.However, its regulatory mechanism remains unclear. In this study, we found that the expression upregulation of the DNA Damage-Inducible Transcript 4(DDIT4) protein, which might play essential roles in TDCIPP-induced neuronal autophagy and apoptosis, was observed in TDCIPP-treated differentiated rat PC12 cells. Furthermore, we determined the protective effect of the DDIT4 suppression on the autophagy and apoptosis induced by TDCIPP using Western blot(WB) and Flow cytometry(FACS) analysis. We observed that TDCIPP treatment increased the DDIT4, the autophagy marker Beclin-1, and the microtubule-associated protein light chain 3-II(LC_(3)II) expressions and decreased the mTOR phosphorylation levels. Conversely, the suppression of DDIT4 expression increased the p-mTOR expression and decreased cell autophagy and apoptosis. Collectively, our results revealed the function of DDIT4 in cell death mechanisms triggered by TDCIPP through the m TOR signaling axis in differentiated PC12 cells. Thus, this study provided vital evidence necessary to explain the mechanism of TDCIPP-induced neurotoxicity in differentiated PC12 cells.展开更多
文摘DDIT3 (DNA Damage-inducible transcript 3),也称为CHOP (C/EBP Homologous Protein)是一种属于CCAAT/增强子结合蛋白家族的转录因子。DDIT3是肿瘤细胞中响应内质网应激和DNA损伤的关键分子。近年来,DDIT3在恶性肿瘤中的研究取得了显著进展,其在多种肿瘤的发生发展中扮演着重要角色。本综述旨在总结DDIT3在恶性肿瘤中的研究进展,探讨DDIT3的异常表达与多肿瘤恶性进展的相关性,以及作为潜在治疗靶点的可能性,为针对肿瘤的深入研究和治疗提供理论依据。DNA Damage-inducible transcript 3 (DDIT3), also known as C/EBP Homologous Protein (CHOP), is a transcription factor belonging to the CCAAT/enhancer-binding protein family. It plays a pivotal role in the cellular stress response pathways, responding to endoplasmic reticulum stress and DNA damage in tumor cells. Recent years have seen significant progress in the study of DDIT3 in malignant tumors, where it plays an important role in the occurrence and development of various cancers. This review aims to summarize the research progress of DDIT3 in malignant tumors, explore the correlation between the abnormal expression of DDIT3 and the malignant progression of multiple tumors, and discuss its potential as a therapeutic target, providing a theoretical basis for in-depth research and treatment of cancer.
基金supported by the National Key Research and Development Program of China (No. 2018YFC1603704)the Tianjin Natural Science Foundation (No. 20JCQNJC00860)。
文摘Tris(1,3-dichloro-2-propyl) phosphate(TDCIPP) is a commonly used organophosphatebased flame retardant and can bio-accumulate in human tissues and organs. As its structure is similar to that of neurotoxic organophosphate pesticides, the neurotoxicity of TDCIPP has raised widespread concerns. TDCIPP can increase neuronal apoptosis and induce autophagy.However, its regulatory mechanism remains unclear. In this study, we found that the expression upregulation of the DNA Damage-Inducible Transcript 4(DDIT4) protein, which might play essential roles in TDCIPP-induced neuronal autophagy and apoptosis, was observed in TDCIPP-treated differentiated rat PC12 cells. Furthermore, we determined the protective effect of the DDIT4 suppression on the autophagy and apoptosis induced by TDCIPP using Western blot(WB) and Flow cytometry(FACS) analysis. We observed that TDCIPP treatment increased the DDIT4, the autophagy marker Beclin-1, and the microtubule-associated protein light chain 3-II(LC_(3)II) expressions and decreased the mTOR phosphorylation levels. Conversely, the suppression of DDIT4 expression increased the p-mTOR expression and decreased cell autophagy and apoptosis. Collectively, our results revealed the function of DDIT4 in cell death mechanisms triggered by TDCIPP through the m TOR signaling axis in differentiated PC12 cells. Thus, this study provided vital evidence necessary to explain the mechanism of TDCIPP-induced neurotoxicity in differentiated PC12 cells.
