hCINAP regulates the DNA-damage response and mediates the resistance of acute myelocytic leukemia cells to therapy

Xu, Ruidan; Yu, Shuyu; Zhu, Dibin; Huang, Xincheng; Xu, Yang; Lao, Yimin; Tian, Yonglu; Zhang, Jinfang; Tang, Zefang; Zhang, Zemin; Yi, Jing; Zhu, Hong‐Hu; Zheng, Xiaofeng

doi:10.1038/s41467-019-11795-5

Cited by 35 publications

(56 citation statements)

References 34 publications

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“…hCINAP knockdown can cause defects in the formation of Cajal bodies, histone transcription and cell viability ( 27 ). In acute myeloid leukemia model mice, hCINAP knockdown results in increased cell death ( 28 ). Furthermore, hCINAP-depleted cells display increased Caspase-3 activities, indicating that apoptosis is one of the reasons for decreased cell viability ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

“…In acute myeloid leukemia model mice, hCINAP knockdown results in increased cell death ( 28 ). Furthermore, hCINAP-depleted cells display increased Caspase-3 activities, indicating that apoptosis is one of the reasons for decreased cell viability ( 28 ). hCINAP knockdown inhibits colorectal cancer stem cell invasion and self-renewal via modulating the activation of LDHA ( 29 ).…”

Section: Introductionmentioning

confidence: 99%

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hCINAP serves a critical role in hypoxia‑induced cardiomyocyte apoptosis via modulating lactate production and mitochondrial‑mediated apoptosis signaling

Xie

Gao

et al. 2020

Mol Med Rep

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acute myocardial infarction (aMi) is a major cause of heart failure and is associated with insufficient myocardial oxygen supply. However, the molecular mechanisms underlying hypoxia-induced cardiomyocyte apoptosis are not completely understood. in the present study, the role of human coilin interacting nuclear aTPase protein (hcinaP) in cardiomyocytes was investigated. ac16 cells were divided into the following four groups: i) Small interfering (si) rna-control (ctrl); (ii) sirna-hcinaP; (iii) empty vector; and (iv) hcinaP-Flag. Protein expression was assessed using western blotting. MTT and apoptosis assays were conducted to detect cell viability and apoptosis, respectively. ccK8 assays and apoptosis assays were used to detect cell viability and apoptosis, respectively. hcinaP promoter activity was examined by luciferase reporter assay. hcinaP expression was induced in a hypoxia-inducible factor-1α-dependent manner under hypoxic conditions. compared with the sirna-ctrl group, hcinaP knockdown inhibited apoptosis, whereas compared with the vector group, hcinaP overexpression increased apoptosis under hypoxic conditions. Mechanistically, compared with the sirna-ctrl group, hcinaP knockdown decreased hypoxia-induced lactate accumulation via regulating lactate dehydrogenase a activity. Moreover, the results indicated that hcinaP was associated with mitochondrial-mediated apoptosis via caspase signaling. collectively, the present study suggested that hcinaP was an important regulator in hypoxia-induced apoptosis and may serve as a promising therapeutic target for aMi.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

hCINAP serves a critical role in hypoxia‑induced cardiomyocyte apoptosis via modulating lactate production and mitochondrial‑mediated apoptosis signaling

Xie

Gao

et al. 2020

Mol Med Rep

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“…(v) Deletion of hCINAP increases NHEJ efficiency. This work suggests that hCINAP is a potential therapeutic target for Acute Myeloid Leukemia given the different response of hCINAP to chemotherapy reagents in normal and AML cells [76]. Their work is an example of the significant outcomes of DNA damage studies for cancer therapeutic strategies.…”

Section: Proximity Ligation Assaymentioning

confidence: 90%

In Situ Detection of Complex DNA Damage Using Microscopy: A Rough Road Ahead

Nikitaki

Pariset

Sudar

et al. 2020

Cancers

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Complexity of DNA damage is considered currently one if not the primary instigator of biological responses and determinant of short and long-term effects in organisms and their offspring. In this review, we focus on the detection of complex (clustered) DNA damage (CDD) induced for example by ionizing radiation (IR) and in some cases by high oxidative stress. We perform a short historical perspective in the field, emphasizing the microscopy-based techniques and methodologies for the detection of CDD at the cellular level. We extend this analysis on the pertaining methodology of surrogate protein markers of CDD (foci) colocalization and provide a unique synthesis of imaging parameters, software, and different types of microscopy used. Last but not least, we critically discuss the main advances and necessary future direction for the better detection of CDD, with important outcomes in biological and clinical setups.

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“…Leukemia, especially acute myeloid leukemia (AML), is a lethal disease characterized by the accumulation of DNA-damaged immature myeloid precursors [ 1 ]. Only around 20% of adult cases are expected to survive past 5 years after diagnosis, and it is a leading cause of cancer death in young adults [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Two Kinds of Iron Nanoparticles as Reactive Oxygen Species Inducer and Scavenger on the Transcriptomic Profiles of Two Human Leukemia Cells with Different Stemness

et al. 2020

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Leukemia is a common and lethal disease. In recent years, iron-based nanomedicines have been developed as a new ferroptosis inducer to leukemia. However, the cytotoxicity of iron nanoparticles to leukemia cells at the transcriptomic level remains unclear. This study investigated the effects of two kinds of iron nanoparticles, 2,3-Dimercaptosuccinic acid (DMSA)-coated Fe3O4 nanoparticles (FeNPs) as a reactive oxygen species (ROS) inducer and Prussian blue nanoparticles (PBNPs) as an ROS scavenger, on the transcriptomic profiles of two leukemia cells (KG1a and HL60) by RNA-Seq. As a result, 470 and 1690 differentially expressed genes (DEGs) were identified in the FeNP-treated HL60 and KG1a cells, respectively, and 2008 and 2504 DEGs were found in the PBNP-treated HL60 and KG1a cells, respectively. Among them, 14 common upregulated and 4 common downregulated DEGs were found, these genes were representative genes that play key roles in lipid metabolism (GBA and ABCA1), iron metabolism (FTL, DNM1, and TRFC), antioxidation (NQO1, GCLM, and SLC7A11), vesicle traffic (MCTP2, DNM1, STX3, and BIN2), and innate immune response (TLR6, ADGRG3, and DDX24). The gene ontology revealed that the mineral absorption pathway was significantly regulated by PBNPs in two cells, whereas the lipid metabolism and HIF-1 signaling pathways were significantly regulated by FeNPs in two cells. This study established the gene signatures of two kinds of nanoparticles in two leukemia cells, which revealed the main biological processes regulated by the two kinds of iron nanoparticles. These data shed new insights into the cytotoxicity of iron nanoparticles that differently regulate ROS in leukemia cells with variant stemness.

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hCINAP regulates the DNA-damage response and mediates the resistance of acute myelocytic leukemia cells to therapy

Cited by 35 publications

References 34 publications

hCINAP serves a critical role in hypoxia‑induced cardiomyocyte apoptosis via modulating lactate production and mitochondrial‑mediated apoptosis signaling

hCINAP serves a critical role in hypoxia‑induced cardiomyocyte apoptosis via modulating lactate production and mitochondrial‑mediated apoptosis signaling

In Situ Detection of Complex DNA Damage Using Microscopy: A Rough Road Ahead

Effects of Two Kinds of Iron Nanoparticles as Reactive Oxygen Species Inducer and Scavenger on the Transcriptomic Profiles of Two Human Leukemia Cells with Different Stemness

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