4-Nitroquinoline-1-oxide effects human lung adenocarcinoma A549 cells by regulating the expression of POLD4

Huang, Qinmiao; Zeng, Yiming; Zhang, Huaping; Lv, Liang-chao; Yang, Dongyong; Lin, Huihuang

doi:10.3892/br.2016.583

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…As reported, POLD4 functioned in cell proliferation and maintenance of genomic stability of human cells [34]. Low expression of POLD4 was reported to weaken the DNA repair systems including nucleotide excision repair and increase the risk of lung cancer formation [35]. Huang et al also reported that POLD4 was low expressed in human lung cancer and was associated with poor prognosis; reduction of POLD4 in lung cancer cells resulted in cell cycle delay, checkpoint activation, and an elevated frequency of chromosomal gap/break formation [36].…”

Section: Discussionmentioning

confidence: 78%

Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway

Zhang

Zhou

et al. 2020

BioMed Research International

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Human gastric cancer is one of the most common malignant tumors with a poor prognosis. Cisplatin (CDDP) is a well-known first-line chemotherapeutic drug. Acquired resistance retards the clinical application of CDDP in gastric cancer. In this study, circular RNA circ_0026359 was demonstrated to be overexpressed in gastric cancer tissues/cells compared with normal gastric tissues/cells and was overexpressed in CDDP-resistant gastric cancer tissues/cells compared with CDDP-sensitive gastric cancer tissues/cells. High levels of circ_0026359 were associated with low overall survival (OS) and relapse-free survival (RFS) rates in gastric cancer patients. circ_0026359 was examined to promote CDDP resistance in gastric cancer cells. circ_0026359 directly interacted and negatively regulated miR-1200. POLD4 was a direct target of miR-1200. miR-1200/POLD4 pathway mediated the promoting role of circ_0026359 in CDDP resistance of gastric cancer. circ_0026359 could be used as a potential target for CDDP-resistant gastric cancer therapy.

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Section: Discussionmentioning

confidence: 78%

Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway

Zhang

Zhou

et al. 2020

BioMed Research International

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“…Huang et al 104 have identified that circAKT3 promotes DNA damage repair via miR-198/PIK3R1. Hsa_circ_0026359 sponges miR-1200 and upregulates POLD4 105 , and low expression of hsa_circ_0026359 has been reported to weaken DNA repair systems 106 . In addition, circPRMT5 overexpression in lung cancer enhances cisplatin resistance by upregulating REV3 L, which encodes the catalytic subunit of DNA polymerase ζ and is responsible for translesional replication 107 .…”

Section: Circrnas Promoting Dna Repair In Chemoresistancementioning

confidence: 99%

Circular RNAs: new biomarkers of chemoresistance in cancer

et al. 2021

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Chemotherapeutics are validated conventional treatments for patients with advanced cancer. However, with continual application of chemotherapeutics, chemoresistance, which is often predictive of poor prognosis, has gradually become a concern in recent years. Circular RNAs (circRNAs), a class of endogenous noncoding RNAs (ncRNAs) with a closed-loop structure, have been reported to be notable targets and markers for the prognosis, diagnosis, and treatment of many diseases, particularly cancer. Although dozens of studies have shown that circRNAs play major roles in drug-resistance activity in tumors, the mechanisms by which circRNAs affect chemoresistance have yet to be explored. In this review, we describe the detailed mechanisms of circRNAs and chemotherapeutics in various cancers and summarize potential therapeutic targets for drug-resistant tumors.

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“…Loss of POLD4 results in a defect in HR and sensitization to PARP inhibitors, indicating that an indispensable component of Polδ is necessary for functional HR [ 14 ]. POLD4 has been observed in the development and progression of multiple cancers, including hepatocellular carcinoma [ 15 ], lung cancer[ 16 , 17 ], and cisplatin resistance in gastric cancer [ 18 ]. In GBMs, POLD4 is associated with cancer patient resistance to radiotherapy and tumor recurrence [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

UCHL3 induces radiation resistance and acquisition of mesenchymal phenotypes by deubiquitinating POLD4 in glioma stem cells

Fan,

You,

Jiang

et al. 2024

Cell. Mol. Life Sci.

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Background The high degree of intratumoral genomic heterogeneity is a major obstacle for glioblastoma (GBM) tumors, one of the most lethal human malignancies, and is thought to influence conventional therapeutic outcomes negatively. The proneural-to-mesenchymal transition (PMT) of glioma stem cells (GSCs) confers resistance to radiation therapy in glioblastoma patients. POLD4 is associated with cancer progression, while the mechanisms underlying PMT and tumor radiation resistance have remained elusive. Method Expression and prognosis of the POLD family were analyzed in TCGA, the Chinese Glioma Genome Atlas (CGGA) and GEO datasets. Tumorsphere formation and in vitro limiting dilution assay were performed to investigate the effect of UCHL3-POLD4 on GSC self-renewal. Apoptosis, TUNEL, cell cycle phase distribution, modification of the Single Cell Gel Electrophoresis (Comet), γ-H2AX immunofluorescence, and colony formation assays were conducted to evaluate the influence of UCHL3-POLD4 on GSC in ionizing radiation. Coimmunoprecipitation and GST pull-down assays were performed to identify POLD4 protein interactors. In vivo, intracranial xenograft mouse models were used to investigate the molecular effect of UCHL3, POLD4 or TCID on GCS. Result We determined that POLD4 was considerably upregulated in MES-GSCs and was associated with a meagre prognosis. Ubiquitin carboxyl terminal hydrolase L3 (UCHL3), a DUB enzyme in the UCH protease family, is a bona fide deubiquitinase of POLD4 in GSCs. UCHL3 interacted with, depolyubiquitinated, and stabilized POLD4. Both in vitro and in vivo assays indicated that targeted depletion of the UCHL3-POLD4 axis reduced GSC self-renewal and tumorigenic capacity and resistance to IR treatment by impairing homologous recombination (HR) and nonhomologous end joining (NHEJ). Additionally, we proved that the UCHL3 inhibitor TCID induced POLD4 degradation and can significantly enhance the therapeutic effect of IR in a gsc-derived in situ xenograft model. Conclusion These findings reveal a new signaling axis for GSC PMT regulation and highlight UCHL3-POLD4 as a potential therapeutic target in GBM. TCID, targeted for reducing the deubiquitinase activity of UCHL3, exhibited significant synergy against MES GSCs in combination with radiation.

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4-Nitroquinoline-1-oxide effects human lung adenocarcinoma A549 cells by regulating the expression of POLD4

Cited by 7 publications

References 18 publications

Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway

Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway

Circular RNAs: new biomarkers of chemoresistance in cancer

UCHL3 induces radiation resistance and acquisition of mesenchymal phenotypes by deubiquitinating POLD4 in glioma stem cells

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