Che-1 gene silencing induces osteosarcoma cell apoptosis by inhibiting mutant p53 expression

Liu, Ming; Wang, Dan; Li, Ning

doi:10.1016/j.bbrc.2016.03.073

Cited by 10 publications

(7 citation statements)

References 31 publications

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“…Thus AATF serves as a critical regulator of p53 driven apoptosis via the p38/MK2/AATF signaling pathway. Consistent with these observations, the silencing of AATF in human osteosarcoma cells inhibited cell proliferation and induced apoptosis by regulating the expression of proapoptotic genes NOXA and PUMA in a p53-dependent manner(Liu et al, 2016).In agreement with the previous findings, AATF is downregulated during the apoptotic process. Investigations by Nicola et al, found that AATF interacts with peptidyl-prolyl isomerase 1 (Pin1), which induces conformational changes affecting the stability of AATF.…”

supporting

confidence: 91%

Section: Aatf and Apoptosismentioning

confidence: 67%

“…Silencing of AATF expression in various breast cancer cell lines decreases mtp53 levels leading to the transactivation of p73 resulting in cell death by the induction of proapoptotic genes (Bruno et al, 2010). In support of this, the deletion of AATF in human osteosarcoma cell lines inhibited cell proliferation and promoted apoptosis by the upregulation of proapoptotic genes such as PUMA and NOXA (Liu et al, 2016). Apart from the proliferative role in cancer cells, AATF has also shown a possible function in sustaining hypoxic conditions in solid tumors leading to poor prognosis even in the advanced cancer stage imparting resistance to chemotherapy.…”

Section: Aatf and Cancermentioning

confidence: 94%

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Emerging roles of AATF: Checkpoint signaling and beyond

Srinivas

Suresh

Mirshahi

et al. 2020

Journal Cellular Physiology

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Apoptosis antagonizing transcription factor (AATF), an interacting partner of RNA polymerase II is a multifunctional protein that is highly conserved in eukaryotes. In addition to the regulation of gene expression as a transcriptional coactivator, AATF is shown to play a dual role in regulating the cell cycle by displacing histone deacetylases 1 (HDAC1) from the retinoblastoma‐E2F transcription factor (Rb‐E2F) complex and also from the specificity protein 1 (Sp1) transcription factor responsible for p21 expression, thereby ensuring cell proliferation and growth arrest, respectively, at different checkpoints of the cell cycle. Notably, AATF has emerged as one of the most important modulators of various cellular responses such as proliferation, apoptosis, and survival. Studies have demonstrated that AATF protects cells from multiple stress stimuli such as DNA damage, ER stress, hypoxia, or glucose deprivation by inducing cell cycle arrest, autophagy, or apoptosis inhibition. Furthermore, AATF serves as a critical regulator in various cancers and promotes tumorigenesis by protecting cancer cells from apoptosis induction, favoring cell proliferation, or promoting cell survival by autophagy. Recent studies have demonstrated the key role of AATF in ribosome biosynthesis and have also provided insights into the mechanistic role of AATF, offering impressive cytoprotection in myocardial infarction, neurologic diseases, and nephronophthisis. In this review, we will provide a comprehensive overview of the role of AATF and shed light on its emerging roles underlining the potential use of AATF as a novel biomarker and as an effective therapeutic target.

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supporting

confidence: 91%

Section: Aatf and Apoptosismentioning

confidence: 67%

Section: Aatf and Cancermentioning

confidence: 94%

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Emerging roles of AATF: Checkpoint signaling and beyond

Srinivas

Suresh

Mirshahi

et al. 2020

Journal Cellular Physiology

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“…Evidence has indicated that increased expression levels of AATF were found in various cancerous tissues and are negatively correlated with patient survival in neuroblastomas (Fanciulli et al ., ; Hopker et al ., ). Moreover, studies have shown that the loss of AATF inhibits proliferation and promotes apoptosis in MG‐63 cells by decreasing the level of mutant p53 (Liu et al ., ). The present study showed that an increased proportion of AATF Delta Ex5 was found in BS008‐treated cells.…”

Section: Discussionmentioning

confidence: 98%

Alternative splicing in human cancer cells is modulated by the amiloride derivative 3,5‐diamino‐6‐chloro‐N‐(N‐(2,6‐dichlorobenzoyl)carbamimidoyl)pyrazine‐2‐carboxide

Lee

Chang

et al. 2019

Molecular Oncology

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Alternative splicing (AS) is a process that enables the generation of multiple protein isoforms with different biological properties from a single mRNA. Cancer cells often use the maneuverability conferred by AS to produce proteins that contribute to growth and survival. In our previous studies, we identified that amiloride modulates AS in cancer cells. However, the effective concentration of amiloride required to modulate AS is too high for use in cancer treatment. In this study, we used computational algorithms to screen potential amiloride derivatives for their ability to regulate AS in cancer cells. We found that 3,5‐diamino‐6‐chloro‐N‐(N‐(2,6‐dichlorobenzoyl)carbamimidoyl)pyrazine‐2‐carboxamide (BS008) can regulate AS of apoptotic gene transcripts, including HIPK3 , SMAC , and BCL‐X , at a lower concentration than amiloride. This splicing regulation involved various splicing factors, and it was accompanied by a change in the phosphorylation state of serine/arginine‐rich proteins (SR proteins). RNA sequencing was performed to reveal that AS of many other apoptotic gene transcripts, such as AATF , ATM , AIFM1 , NFKB1 , and API5 , was also modulated by BS008. In vivo experiments further indicated that treatment of tumor‐bearing mice with BS008 resulted in a marked decrease in tumor size. BS008 also had inhibitory effects in vitro , either alone or in a synergistic combination with the cytotoxic chemotherapeutic agents sorafenib and nilotinib. BS008 enabled sorafenib dose reduction without compromising antitumor activity. These findings suggest that BS008 may possess therapeutic potential for cancer treatment.

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“…Therefore, NOP2 and GTPBP4 may be associated with the progress of sepsis. The AATF protein, also known as Che-1, is encoded by the AATF gene, which is involved in cell apoptosis ( 33 ). The overexpression of AATF interferes with MAP3K12/DLK (a protein kinase)-induced apoptosis ( 34 , 35 ), which forms heterodimers with a leucine zipper containing TFs, including MYC, and has a regulatory role ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential genes and miRNAs associated with sepsis based on microarray analysis

et al. 2018

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Sepsis is a type of systemic inflammatory response syndrome caused by infection. The present study aimed to examine key genes and microRNAs (miRNAs) involved in the pathogenesis of sepsis. The GSE13205 microarray dataset, downloaded from the Gene Expression Omnibus was analyzed using bioinformatics tools, and included muscle biopsy specimens of 13 patients with sepsis and eight healthy controls. The differentially expressed genes (DEGs) in samples from patients with sepsis were identified using the Linear Models for Microarray package in R language. Using the Database for Annotation, Visualization and Integration Discovery tool, functional and pathway enrichment analyses were performed to examine the potential functions of the DEGs. The protein-protein interaction (PPI) network was constructed with the DEGs using the Search Tool for the Retrieval of Interacting Genes, and the network topology was analyzed using CytoNCA. Subsequently, MCODE in Cytoscape was used to identify modules in the PPI network. Finally, the integrated regulatory network was constructed based on the DEGs, miRNAs and transcription factors (TFs). A total of 259 upregulated DEGs (MYC and BYSL) and 204 downregulated DEGs were identified in the patients with sepsis. NOP14, NOP2, AATF, GTPBP4, BYSL and TRMT6 were key genes in the MCODE module. In the integrated DEG-miRNA-TF regulatory network, hsa-miR-150 (target gene MYLK3) and 21 TFs, comprising 14 upregulated DEGs (including MYC) and seven downregulated DEGs, were identified. The results suggested that NOP14, NOP2, AATF, GTPBP4, BYSL, MYC, MYLK3 and miR-150 may be involved in the pathogenesis of sepsis.

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Che-1 gene silencing induces osteosarcoma cell apoptosis by inhibiting mutant p53 expression

Cited by 10 publications

References 31 publications

Emerging roles of AATF: Checkpoint signaling and beyond

Emerging roles of AATF: Checkpoint signaling and beyond

Alternative splicing in human cancer cells is modulated by the amiloride derivative 3,5‐diamino‐6‐chloro‐N‐(N‐(2,6‐dichlorobenzoyl)carbamimidoyl)pyrazine‐2‐carboxide

Identification of potential genes and miRNAs associated with sepsis based on microarray analysis

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