Association of <i>PARP1</i> polymorphisms with response to chemotherapy in patients with high‐risk neuroblastoma

Avitabile, Marianna; Lasorsa, Vito Alessandro; Cantalupo, Sueva; Cardinale, Antonella; Cimmino, Flora; Montella, Annalaura; Capasso, Dalila; Haupt, Riccardo; Amoroso, Loredana; Garaventa, Alberto; Quattrone, Alessandro; Corrias, Maria Valeria; Iolascon, Achille; Capasso, Mario

doi:10.1111/jcmm.15058

Cited by 12 publications

(12 citation statements)

References 56 publications

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“…The prognosis of patients with NB is extremely poor, which accounts for ~12–15% of all pediatric cancer-associated deaths ( 7 , 8 ). In recent years, treatments for low- and medium-risk NB have improved; however, the cure rate for patients with high-risk NB remains low ( 9 , 10 ). It is therefore crucial to develop novel treatments for patients with high-risk NB.…”

Section: Introductionmentioning

confidence: 99%

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

Xie

Zhang

et al. 2020

Oncol Lett

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Neuroblastoma (NB) is the most common type of extracranial solid tumor found in children. Despite several treatment options, patients with advanced stage disease have a poor prognosis. Previous studies have reported that enhancer of zeste homolog 2 (EZH2) and long non-coding RNAs (lncRNAs) have abnormal expression levels in NB and participate in tumorigenesis and NB development. However, the association between EZH2 and lncRNAs remain unclear. In the present study, RNA immunoprecipitation-sequencing (RIP-seq) was used to analyze the lncRNAs binding to EZH2. Following EZH2 knockdown via short hairpin RNA, RNA-seq was performed in shEZH2 and control groups in SH-SY5Y cells. Chromatin IP (ChIP)-seq was used to determine the genes that may be regulated by EZH2. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to identify the signaling pathways involved in NB. The results from RIP-seq identified 94 lncRNAs, including SNHG7, SNHG22, KTN-AS1 and Linc00843. Furthermore, results from RNA-seq demonstrated that, following EZH2 knockdown, 448 genes were up-and 571 genes were downregulated, with 32 lncRNAs up-and 35 downregulated and differentially expressed compared with control groups. Certain lncRNAs, including MALAT1, H19, Linc01021 and SNHG5, were differentially expressed in EZH2-knockdown group compared with the control group. ChIP-seq identified EZH2 located in the promoter region of 138 lncRNAs including CASC16, CASC15, LINC00694 and TBX5-AS1. In summary, the present study demonstrated that certain lncRNAs directly bound EZH2 and regulated EZH2 expression levels. A number of these lncRNAs that are associated with EZH2 may participate in NB tumorigenesis.

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Section: Introductionmentioning

confidence: 99%

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

Xie

Zhang

et al. 2020

Oncol Lett

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“…Hu et al studied the mechanism of chemotherapeutic drug resistance and found that PARP1 induced the degradation of BRD7, leading to the resistance of cancer cells to DNA damage agents [43]. Avitabile et al found that PARP1 was one of the main DNA damage sensors involved in DNA repair system and genomic stability, and PARP1 expression is closely related to chemotherapy resistance of neuroblastoma [44]. BER is a very important pathway leading to oxaliplatin resistance [45].…”

Section: Discussionmentioning

confidence: 99%

METTL3 promotes oxaliplatin resistance of gastric cancer CD133+ stem cells by promoting PARP1 mRNA stability

Wang

Lan

et al. 2022

Cell. Mol. Life Sci.

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Oxaliplatin is the first-line regime for advanced gastric cancer treatment, while its resistance is a major problem that leads to the failure of clinical treatments. Tumor cell heterogeneity has been considered as one of the main causes for drug resistance in cancer. In this study, the mechanism of oxaliplatin resistance was investigated through in vitro human gastric cancer organoids and gastric cancer oxaliplatin-resistant cell lines and in vivo subcutaneous tumorigenicity experiments. The in vitro and in vivo results indicated that CD133+ stem cell-like cells are the main subpopulation and PARP1 is the central gene mediating oxaliplatin resistance in gastric cancer. It was found that PARP1 can effectively repair DNA damage caused by oxaliplatin by means of mediating the opening of base excision repair pathway, leading to the occurrence of drug resistance. The CD133+ stem cells also exhibited upregulated expression of N6-methyladenosine (m6A) mRNA and its writer METTL3 as showed by immunoprecipitation followed by sequencing and transcriptome analysis. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3′-untranslated Region (3′-UTR) of PARP1 mRNA. The CD133+ tumor stem cells can regulate the stability and expression of m6A to PARP1 through METTL3, and thus exerting the PARP1-mediated DNA damage repair ability. Therefore, our study demonstrated that m6A Methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity.

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“…The present and previous results (21) indicate that C282Y HFE impacts neuroblastoma characteristics such as therapy resistance and cell proliferation. Several studies reported that single nucleotide polymorphisms (SNPs) in genes [e.g., ATP binding cassette subfamily C member 1 (ABCC1); caspase 8 (CASP8); ERCC excision repair 1, endonuclease non-catalytic subunit/ERCC excision repair 4, endonuclease non-catalytic subunit (ERCC1/XPF or ERCC1/ERCC4); poly(ADP-ribose) polymerase 1 (PARP1); base excision repair (BER); methyltransferase like 14 (METTL14)] are risk factors for neuroblastoma development and patient survival (40)(41)(42)(43)(44)(45). Our data indicate that the frequency of the C282Y HFE SNP in neuroblastoma patients should also be determined in future clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Biological Activity of a Thiobarbituric Acid Compound in Neuroblastomas

et al. 2021

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Background/Aim: We have previously reported the identification of the cytotoxic chemotype compound-I (CC-I) from a chemical library screening against glioblastoma. Materials and Methods: The biological activity of CC-I on drug-resistant neuroblastomas [e.g., HFE gene variant C282Y stably transfected human neuroblastoma SH-SY5Y cells (C282Y HFE/SH-SY5Y), SK-N-AS] was characterized using cell culture models and in vivo mouse tumor models. Results: CC-I had potent cytotoxicity on therapy-resistant neuroblastoma cells and limited cytotoxicity on human primary dermal fibroblast cells. In addition, CC-I showed a robust anti-tumor effect on therapyresistant human neuroblastoma C282Y HFE/SH-SY5Y cells but not on SK-N-AS cells in a subcutaneous tumor model. CC-I induced phosphorylation of heat shock protein 27 (HSP27), protein kinase B (Akt), and c-Jun N-terminal kinase (JNK) in C282Y HFE/SH-SY5Y neuroblastoma cells. Conclusion: CC-I may be an effective therapeutic option for therapy-resistant neuroblastomas, especially if they express the C282Y HFE gene variant. Its anti-tumor effects are possibly through HSP27-Akt-JNK activation. Neuroblastoma is the second most common solid tumor discovered in children (1). It begins in the nerve cells outside of the brain, most often in the adrenal glands located on top of both kidneys. Nearly 90% of neuroblastomas are diagnosed by age 10 (2). In the United States, neuroblastoma occurs in about 800 children (age up to 14) each year, which accounts for 6% of all childhood cancers (3). The International Neuroblastoma Risk Group Staging System was developed by the International Neuroblastoma Risk Group for the standardization of neuroblastoma risk classification and for clinical trials (4). Risk factors for neuroblastoma include age at diagnosis, disease stage, tumor histology, and N-myc proto-oncogene protein (MYCN) amplification status (5). Although the 5-year survival rate for low-risk neuroblastoma is 95%, the 5-year survival rate for high-risk neuroblastoma is only 40-50% (3). About half of the neuroblastomas are metastatic at diagnosis, and advanced disease remains difficult to treat successfully despite the aggressive multimodality therapy. Treatment for neuroblastoma usually involves a variety of approaches such as chemotherapy, radiation, surgery, stem cell transplantation, biological agents, and immunotherapy (6, 7). The majority of patients with high-risk neuroblastoma will relapse despite receiving aggressive multimodal therapy, while an additional 10% to 20% will be refractory to induction therapy (8, 9). Because of disease heterogeneity among highrisk cases, subsequent management with salvage chemotherapy can be very challenging. Therefore, developing new treatment agents against neuroblastoma, especially therapy-resistant neuroblastoma, is urgently needed. We previously reported the identification of compound CC-I, a thiobarbituric acid derivative, from the screening of the ChemBridge small molecule library compounds, as an effective agent against drug-resistant glioblasto...

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Association of PARP1 polymorphisms with response to chemotherapy in patients with high‐risk neuroblastoma

Cited by 12 publications

References 56 publications

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

METTL3 promotes oxaliplatin resistance of gastric cancer CD133+ stem cells by promoting PARP1 mRNA stability

Biological Activity of a Thiobarbituric Acid Compound in Neuroblastomas

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