ZNF830 mediates cancer chemoresistance through promoting homologous-recombination repair

Chen, Guo; Chen, Jianxiang; Qiao, Yiting; Shi, Yaru; Liu, Wei; Zeng, Qi; Xie, Hui; Shi, Xiaorui; Sun, Yao; Liu, Xu; Li, Tongyu; Zhou, Liqian; Wan, Jianqin; Xie, Tian; Wang, Hangxiang; Wang, Fu

doi:10.1093/nar/gkx1258

Cited by 40 publications

(37 citation statements)

References 46 publications

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“…These results suggest that ZNF281 levels could be used to predict patients' responsiveness to DNA-damaging treatments. In line with this finding, another zinc finger protein, ZNF830, has been recently implied in the chemoresistance to genotoxic therapies, as a consequence of its role in promoting DNA repair by HR [36]. Furthermore, the strong correlation between ZNF281 recruitment and PARP activity (Fig.…”

Section: Discussionsupporting

confidence: 66%

ZNF281 is recruited on DNA breaks to facilitate DNA repair by non-homologous end joining

et al. 2019

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Efficient repair of DNA double-strand breaks (DSBs) is of critical importance for cell survival. Although non-homologous end joining (NHEJ) is the most used DSBs repair pathway in the cells, how NHEJ factors are sequentially recruited to damaged chromatin remains unclear. Here, we identify a novel role for the zinc-finger protein ZNF281 in participating in the ordered recruitment of the NHEJ repair factor XRCC4 at damage sites. ZNF281 is recruited to DNA lesions within seconds after DNA damage through a mechanism dependent on its DNA binding domain and, at least in part, on poly-ADP ribose polymerase (PARP) activity. ZNF281 binds XRCC4 through its zinc-finger domain and facilitates its recruitment to damaged sites. Consequently, depletion of ZNF281 impairs the efficiency of the NHEJ repair pathway and decreases cell viability upon DNA damage. Survival analyses from datasets of commonly occurring human cancers show that higher levels of ZNF281 correlate with poor prognosis of patients treated with DNA-damaging therapies. Thus, our results define a late ZNF281-dependent regulatory step of NHEJ complex assembly at DNA lesions and suggest additional possibilities for cancer patients’ stratification and for the development of personalised therapeutic strategies.

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Section: Discussionsupporting

confidence: 66%

ZNF281 is recruited on DNA breaks to facilitate DNA repair by non-homologous end joining

et al. 2019

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“…Indeed, pharmacological inhibition of CDK1/2 sensitizes glioblastoma cells to temozolomide [53]. A recent study demonstrated that zinc finger protein 830 (ZNF830) plays a role in the repair of DNA double-strand breaks and that knockdown of ZNF830 sensitizes lung cancer cells to olaparib, a DNA-damaging agent [54]. In addition, the importance of miRNAs in the regulation of DNA repair mechanisms has been underscored.…”

Section: Dna Damage Repair In Cancermentioning

confidence: 99%

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

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The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.Cells 2020, 9, 29 2 of 32 to confer the ability to acquire CSC properties onto cancer cells, thereby contributing to therapeutic resistance [7]. Moreover, cell-to-cell communication via extracellular vesicles among different types of cells within the cancer microenvironment could affect the efficacy of cancer therapies by delivering miRNAs that regulate various signaling pathways connected to therapeutic resistance [8,9].Combination therapies have been proposed to overcome therapeutic resistance via the combined inhibition of different mechanisms. For example, the combination of cobimetinib and pictilisib was reported to be beneficial for the treatment of colorectal cancer cells. However, resistance is unavoidable even after the combination treatment [10]. Similarly, the simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and a mechanistic target of rapamycin kinase (mTOR) was reported to activate extracellular signal-regulated kinase (ERK), a pro-survival factor, in acute myeloid leukemia [11]. Therefore, it is still necessary to explore new combination strategies to defeat therapeutic resistance. An improved understanding of the cellular basis of cancer therapeutic resistance can further provide promising opportunities to design and develop novel cancer treatment strategies to manage cancers.MicroRNAs (miRNAs) are widely recognized, small, regulatory RNAs modulating numerous intracellular signaling pathways in several diseases, including cancers. Based on the expression levels and intracellular functions of miRNAs, they could act as tumor-suppressive or oncogenic factors in cancer cells [12][13][14]. The abnormal expression of miRNAs is associated with therapeutic resistance in cancer, and the modulation of m...

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“…Now the data are included in BioStudies database, which is a public health database. Our study did not require the approval of an ethics committee as it is a secondary analysis of BioStudies database of a public database and of free access (Alarconruiz, Heredia & Tayperondan, 2019;Sarkans et al, 2018). This article does not contain any studies with human participants or animals performed by any of our authors.…”

Section: Additional Information and Declarations Fundingmentioning

confidence: 99%

A comparative study of machine learning algorithms for predicting acute kidney injury after liver cancer resection

Lei

Wang

Xue

et al. 2020

PeerJ

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Objective Machine learning methods may have better or comparable predictive ability than traditional analysis. We explore machine learning methods to predict the likelihood of acute kidney injury after liver cancer resection. Methods This is a secondary analysis cohort study. We reviewed data from patients who had undergone resection of primary hepatocellular carcinoma between January 2008 and October 2015. Results The analysis included 1,173 hepatectomy patients, 77 (6.6%) of whom had AKI and 1,096 (93.4%) who did not. The importance matrix for the Gbdt algorithm model shows that age, cholesterol, tumor size, surgery duration and PLT were the five most important parameters. Figure 1 shows that Age, tumor size and surgery duration had weak positive correlations with AKI. Cholesterol and PLT also had weak negative correlations with AKI. The models constructed by the four machine learning algorithms in the training group were compared. Among the four machine learning algorithms, random forest and gbm had the highest accuracy, 0.989 and 0.970 respectively. The precision of four of the five algorithms was 1, random forest being the exception. Among the test group, gbm had the highest accuracy (0.932). Random forest and gbm had the highest precision, both being 0.333. The AUC values for the four algorithms were: Gbdt (0.772), gbm (0.725), forest (0.662) and DecisionTree (0.628). Conclusions Machine learning technology can predict acute kidney injury after hepatectomy. Age, cholesterol, tumor size, surgery duration and PLT influence the likelihood and development of postoperative acute kidney injury.

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ZNF830 mediates cancer chemoresistance through promoting homologous-recombination repair

Cited by 40 publications

References 46 publications

ZNF281 is recruited on DNA breaks to facilitate DNA repair by non-homologous end joining

ZNF281 is recruited on DNA breaks to facilitate DNA repair by non-homologous end joining

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

A comparative study of machine learning algorithms for predicting acute kidney injury after liver cancer resection

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