Zinc finger protein 668 interacts with Tip60 to promote H2AX acetylation after DNA damage

Hu, Ruiming; Wang, Edward; Peng, Guang; Dai, Hui; Lin, Shiaw Yih

doi:10.4161/cc.25064

Cited by 19 publications

(19 citation statements)

References 42 publications

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“…4a,b ; Supplementary Table 6 ). Oncogenes validated within the cerebrum included: ZNF668 that links chromatin relaxation state to DNA repair 10 and BCL7C a member of the SWI/SNF chromatin regulatory complex 11 (both among 23 candidates in the 16p11.2 amplicon; Supplementary Table 1 ); RAB3A that controls late stage vesicle trafficking and exocytosis in neuronal cells 12 , 13 (among 7 candidates in the 19p13.11 amplicon); the putative oncogene PRDX2 that regulates oxidation-induced apoptosis 14 , and RTBDN of unknown function (both among 25 candidates in the 19p13.13 amplicon); and the AKT2 oncogene (among four candidates in the 19q13.2 amplicon; Fig. 4a ).…”

Section: Resultsmentioning

confidence: 99%

An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes

et al. 2015

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Cancers are characterized by non-random, chromosome copy number alterations that presumably contain oncogenes and tumor–suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here, we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models we validate eight new ependymoma oncogenes and 10 ependymoma TSGs that converge on a small number of cell functions including vesicle trafficking, DNA modification and cholesterol biosynthesis, pinpointing these as potential new therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes

et al. 2015

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“…To induce DSBs, we subjected the cells to ionizing radiation (IR, 10 Gy) and performed immunofluorescence staining as described previously (28). Cells were treated with cytoskeleton and stripping buffers, fixed with 4% paraformaldehyde, and subjected to permeabilization with 0.5% NP-40 and 1% Triton X-100.…”

Section: Methodsmentioning

confidence: 99%

mTOR Inhibitors Suppress Homologous Recombination Repair and Synergize with PARP Inhibitors via Regulating SUV39H1 in BRCA-Proficient Triple-Negative Breast Cancer

Liu

Lin

et al. 2016

Clinical Cancer Research

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104

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Purpose Triple-negative breast cancer (TNBC) is a highly heterogeneous disease and has the worst outcome among all subtypes of breast cancers. Although PARP inhibitors represent a promising treatment in TNBC with BRCA1/BRCA2 mutations, there is great interest in identifying drug combinations that can extend the utility of PARP inhibitors to a majority of TNBC patients with wild-type BRCA1/BRCA2. Here we explored whether mTOR inhibitors, through modulating homologous recombination (HR) repair, would provide therapeutic benefit in combination with PARP inhibitors in preclinical models of BRCA-proficient TNBC. Experimental Design We have studies the effects of mTOR inhibitors on HR repair following DNA double-strand breaks (DSBs). We further demonstrated the in vitro and in vivo activities of combined treatment of mTOR inhibitors with PARP inhibitors in BRCA-proficient TNBC. Moreover, microarray analysis and rescue experiments were employed to investigate the molecular mechanisms of action. Results We found that mTOR inhibitors significantly suppressed HR repair in two BRCA-proficient TNBC cell lines. mTOR inhibitors and PARP inhibitors in combination exhibited strong synergism against these TNBC cell lines. In TNBC xenografts, we observed enhanced efficacy of everolimus in combination with talazoparib (BMN673) compared with either drug alone. We further identified through microarray analysis and by rescue assays that mTOR inhibitors suppressed HR repair and synergized with PARP inhibitors through regulating the expression of SUV39H1 in BRCA-proficient TNBCs. Conclusions Collectively, these findings strongly suggest that combining mTOR inhibitors and PARP inhibitors would be an effective therapeutic approach to treat BRCA-proficient TNBC patients.

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“…ZNF668 has been characterized as a breast tumor suppressor gene that regulates p53 stability by binding to the mouse double minute 2 homolog (MDM2) (9). ZNF668 has also been demonstrated to mediate Tip60 acetylation and ionizing radiation-induced hyperacetylation of H2A histone family member X following DNA damage (10). Nevertheless, to the best of our knowledge, the effect of ZNF668 on invasion and metastasis of human tumors has not been determined to date.…”

Section: Introductionmentioning

confidence: 92%

Zinc finger protein 668 suppresses non-small cell lung cancer invasion and migration by downregulating Snail and upregulating E-cadherin and zonula occludens-1

Zhang

Jiang

et al. 2018

Oncol Lett

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Abstract. Zinc finger protein 668 (ZNF668) is a recently discovered protein and its expression levels, as well as its involvement in the invasion and metastasis of non-small cell lung cancer (NSCLC), are largely unknown. In the present study, immunohistochemical analysis demonstrated that ZNF668 protein expression was decreased in lung tumors (51/167, 30.5%) compared with adjacent normal lung tissues (43/62, 69.4%; P<0.001). Subsequent statistical analysis revealed that ZNF668 expression was negatively associated with increased tumor-node-metastasis stage (P=0.019) and lymph node metastasis (P=0.002). Following ZNF668 downregulation by transfection of a ZNF668-expressing plasmid or small interfering RNA, it was demonstrated that ZNF668 inhibited the invasion and migration of NSCLC cells. Furthermore, restoration of ZNF668 expression downregulated the expression of Snail and increased the protein levels of epithelial (E-)cadherin and zonula occludens-1 (ZO-1). The results of the present study suggest that ZNF668 is downregulated in human NSCLC. Furthermore, restoration of ZNF668 expression was demonstrated to decrease the expression of Snail and increase the expression of E-cadherin and ZO-1, suppressing the invasion and migration of NSCLC cells.

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Zinc finger protein 668 interacts with Tip60 to promote H2AX acetylation after DNA damage

Cited by 19 publications

References 42 publications

An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes

An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes

mTOR Inhibitors Suppress Homologous Recombination Repair and Synergize with PARP Inhibitors via Regulating SUV39H1 in BRCA-Proficient Triple-Negative Breast Cancer

Zinc finger protein 668 suppresses non-small cell lung cancer invasion and migration by downregulating Snail and upregulating E-cadherin and zonula occludens-1

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