NAR Cancer最新文献_第5页

Correction to 'The DNA repair function of BCL11A suppresses senescence and promotes continued proliferation of triple-negative breast cancer cells'. 修正“BCL11A的DNA修复功能抑制衰老并促进三阴性乳腺癌细胞的持续增殖”。

NAR Cancer Pub Date : 2023-03-01 DOI: 10.1093/narcan/zcad008

引用次数: 0

Mono-ADP-ribosylation by PARP10 and PARP14 in genome stability. PARP10和PARP14在基因组稳定性中的单ADP-核糖基化作用

NAR Cancer Pub Date : 2023-02-20 eCollection Date: 2023-03-01 DOI: 10.1093/narcan/zcad009

Ashna Dhoonmoon, Claudia M Nicolae

{"title":"Mono-ADP-ribosylation by PARP10 and PARP14 in genome stability.","authors":"Ashna Dhoonmoon, Claudia M Nicolae","doi":"10.1093/narcan/zcad009","DOIUrl":"10.1093/narcan/zcad009","url":null,"abstract":"ADP-ribosylation is a post-translational modification involved in a variety of processes including DNA damage repair, transcriptional regulation, and cellular proliferation. Depending on the number of ADP moieties transferred to target proteins, ADP-ribosylation can be classified either as mono-ADP-ribosylation (MARylation) or poly-ADP-ribosylation (PARylation). This post-translational modification is catalyzed by enzymes known as ADP-ribosyltransferases (ARTs), which include the poly (ADP-ribose)-polymerase (PARP) superfamily of proteins. Certain members of the PARP family including PARP1 and PARP2 have been extensively studied and assessed as therapeutic targets. However, the other members of the PARP family of protein are not as well studied but have gained attention in recent years given findings suggesting their roles in an increasing number of cellular processes. Among these other members are PARP10 and PARP14, which have gradually emerged as key players in maintenance of genomic stability and carcinogenesis. PARP10 and PARP14 catalyze the transfer of a single ADP moiety to target proteins. Here, we summarize the current knowledge on MARylation in DNA repair and cancer, focusing on PARP10 and PARP14. We highlight the roles of PARP10 and PARP14 in cancer progression and response to chemotherapeutics and briefly discuss currently known PARP10 and PARP14 inhibitors.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9940457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9759076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Roles of trans-lesion synthesis (TLS) DNA polymerases in tumorigenesis and cancer therapy. 反式离子合成（TLS）DNA 聚合酶在肿瘤发生和癌症治疗中的作用。

NAR Cancer Pub Date : 2023-02-06 eCollection Date: 2023-03-01 DOI: 10.1093/narcan/zcad005

Jay Anand, Lilly Chiou, Carly Sciandra, Xingyuan Zhang, Jiyong Hong, Di Wu, Pei Zhou, Cyrus Vaziri

{"title":"Roles of trans-lesion synthesis (TLS) DNA polymerases in tumorigenesis and cancer therapy.","authors":"Jay Anand, Lilly Chiou, Carly Sciandra, Xingyuan Zhang, Jiyong Hong, Di Wu, Pei Zhou, Cyrus Vaziri","doi":"10.1093/narcan/zcad005","DOIUrl":"10.1093/narcan/zcad005","url":null,"abstract":"DNA damage tolerance and mutagenesis are hallmarks and enabling characteristics of neoplastic cells that drive tumorigenesis and allow cancer cells to resist therapy. The 'Y-family' trans-lesion synthesis (TLS) DNA polymerases enable cells to replicate damaged genomes, thereby conferring DNA damage tolerance. Moreover, Y-family DNA polymerases are inherently error-prone and cause mutations. Therefore, TLS DNA polymerases are potential mediators of important tumorigenic phenotypes. The skin cancer-propensity syndrome xeroderma pigmentosum-variant (XPV) results from defects in the Y-family DNA Polymerase Pol eta (Polη) and compensatory deployment of alternative inappropriate DNA polymerases. However, the extent to which dysregulated TLS contributes to the underlying etiology of other human cancers is unclear. Here we consider the broad impact of TLS polymerases on tumorigenesis and cancer therapy. We survey the ways in which TLS DNA polymerases are pathologically altered in cancer. We summarize evidence that TLS polymerases shape cancer genomes, and review studies implicating dysregulated TLS as a driver of carcinogenesis. Because many cancer treatment regimens comprise DNA-damaging agents, pharmacological inhibition of TLS is an attractive strategy for sensitizing tumors to genotoxic therapies. Therefore, we discuss the pharmacological tractability of the TLS pathway and summarize recent progress on development of TLS inhibitors for therapeutic purposes.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/65/zcad005.PMC9900426.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10062219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

APE2: catalytic function and synthetic lethality draw attention as a cancer therapy target. APE2：催化功能和合成致死性引起人们对癌症治疗靶点的关注。

NAR Cancer Pub Date : 2023-02-06 eCollection Date: 2023-03-01 DOI: 10.1093/narcan/zcad006

Anne McMahon, Jianjun Zhao, Shan Yan

{"title":"APE2: catalytic function and synthetic lethality draw attention as a cancer therapy target.","authors":"Anne McMahon, Jianjun Zhao, Shan Yan","doi":"10.1093/narcan/zcad006","DOIUrl":"10.1093/narcan/zcad006","url":null,"abstract":"AP endonuclease 2 (APE2, APEX2 or APN2) is an emerging critical protein involved in genome and epigenome integrity. Whereas its catalytic function as a nuclease in DNA repair is widely accepted, recent studies have elucidated the function and mechanism of APE2 in the immune response and DNA damage response. Several genome-wide screens have identified APE2 as a synthetic lethal target for deficiencies of BRCA1, BRCA2 or TDP1 in cancer cells. Due to its overexpression in several cancer types, APE2 is proposed as an oncogene and could serve as prognostic marker of overall survival of cancer treatment. However, it remains to be discovered whether and how APE2 catalytic function and synthetic lethality can be modulated and manipulated as a cancer therapy target. In this review, we provide a current understanding of alterations and expression of APE2 in cancer, the function of APE2 in the immune response, and mechanisms of APE2 in ATR/Chk1 DNA damage response. We also summarize the role of APE2 in DNA repair pathways in the removal of heterogenous and complexed 3'-termini and MMEJ. Finally, we provide an updated perspective on how APE2 may be targeted for cancer therapy and future directions of APE2 studies in cancer biology.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9759056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumor-suppressive disruption of cancer subtype-associated super enhancer circuits by small molecule treatment. 通过小分子治疗破坏与癌症亚型相关的超级增强子回路，从而抑制肿瘤。

NAR Cancer Pub Date : 2023-02-06 eCollection Date: 2023-03-01 DOI: 10.1093/narcan/zcad007

Anke Koeniger, Pierfrancesco Polo, Anna Brichkina, Florian Finkernagel, Alexander Visekruna, Andrea Nist, Thorsten Stiewe, Michael Daude, Wibke E Diederich, Thomas M Gress, Till Adhikary, Matthias Lauth

{"title":"Tumor-suppressive disruption of cancer subtype-associated super enhancer circuits by small molecule treatment.","authors":"Anke Koeniger, Pierfrancesco Polo, Anna Brichkina, Florian Finkernagel, Alexander Visekruna, Andrea Nist, Thorsten Stiewe, Michael Daude, Wibke E Diederich, Thomas M Gress, Till Adhikary, Matthias Lauth","doi":"10.1093/narcan/zcad007","DOIUrl":"10.1093/narcan/zcad007","url":null,"abstract":"Transcriptional cancer subtypes which correlate with traits such as tumor growth, drug sensitivity or the chances of relapse and metastasis, have been described for several malignancies. The core regulatory circuits (CRCs) defining these subtypes are established by chromatin super enhancers (SEs) driving key transcription factors (TFs) specific for the particular cell state. In neuroblastoma (NB), one of the most frequent solid pediatric cancer entities, two major SE-directed molecular subtypes have been described: A more lineage-committed adrenergic (ADRN) and a mesenchymal (MES) subtype. Here, we found that a small isoxazole molecule (ISX), a frequently used pro-neural drug, reprogrammed SE activity and switched NB cells from an ADRN subtype towards a growth-retarded MES-like state. The MES-like state shared strong transcriptional overlap with ganglioneuroma (GN), a benign and highly differentiated tumor of the neural crest. Mechanistically, ISX suppressed chromatin binding of N-MYC, a CRC-amplifying transcription factor, resulting in loss of key ADRN subtype-enriched components such as N-MYC itself, PHOX2B and ALK, while concomitently, MES subtype markers were induced. Globally, ISX treatment installed a chromatin accessibility landscape typically associated with low risk NB. In summary, we provide evidence that CRCs and cancer subtype reprogramming might be amenable to future therapeutic targeting.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10684759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ku-DNA binding inhibitors modulate the DNA damage response in response to DNA double-strand breaks. Ku-DNA结合抑制剂调节对DNA双链断裂的DNA损伤反应。

NAR Cancer Pub Date : 2023-02-06 eCollection Date: 2023-03-01 DOI: 10.1093/narcan/zcad003

Pamela L Mendoza-Munoz, Navnath S Gavande, Pamela S VanderVere-Carozza, Katherine S Pawelczak, Joseph R Dynlacht, Joy E Garrett, John J Turchi

{"title":"Ku-DNA binding inhibitors modulate the DNA damage response in response to DNA double-strand breaks.","authors":"Pamela L Mendoza-Munoz, Navnath S Gavande, Pamela S VanderVere-Carozza, Katherine S Pawelczak, Joseph R Dynlacht, Joy E Garrett, John J Turchi","doi":"10.1093/narcan/zcad003","DOIUrl":"10.1093/narcan/zcad003","url":null,"abstract":"The DNA-dependent protein kinase (DNA-PK) plays a critical role in the DNA damage response (DDR) and non-homologous end joining (NHEJ) double-strand break (DSB) repair pathways. Consequently, DNA-PK is a validated therapeutic target for cancer treatment in certain DNA repair-deficient cancers and in combination with ionizing radiation (IR). We have previously reported the discovery and development of a novel class of DNA-PK inhibitors with a unique mechanism of action, blocking the Ku 70/80 heterodimer interaction with DNA. These Ku-DNA binding inhibitors (Ku-DBi's) display nanomolar activity in vitro, inhibit cellular DNA-PK, NHEJ-catalyzed DSB repair and sensitize non-small cell lung cancer (NSCLC) cells to DSB-inducing agents. In this study, we demonstrate that chemical inhibition of the Ku-DNA interaction potentiates the cellular effects of bleomycin and IR via p53 phosphorylation through the activation of the ATM pathway. This response is concomitant with a reduction of DNA-PK catalytic subunit (DNA-PKcs) autophosphorylation at S2056 and a time-dependent increase in H2AX phosphorylation at S139. These results are consistent with Ku-DBi's abrogating DNA-PKcs autophosphorylation to impact DSB repair and DDR signaling through a novel mechanism of action, and thus represent a promising anticancer therapeutic strategy in combination with DNA DSB-inducing agents.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10684758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CAFuncAPA: a knowledgebase for systematic functional annotations of APA events in human cancers. CAFuncAPA：人类癌症APA事件的系统功能注释的知识库。

NAR Cancer Pub Date : 2023-01-23 eCollection Date: 2023-03-01 DOI: 10.1093/narcan/zcad004

Kexin Huang, Sijia Wu, Xiaotong Yang, Tiangang Wang, Xi Liu, Xiaobo Zhou, Liyu Huang

{"title":"CAFuncAPA: a knowledgebase for systematic functional annotations of APA events in human cancers.","authors":"Kexin Huang, Sijia Wu, Xiaotong Yang, Tiangang Wang, Xi Liu, Xiaobo Zhou, Liyu Huang","doi":"10.1093/narcan/zcad004","DOIUrl":"10.1093/narcan/zcad004","url":null,"abstract":"Alternative polyadenylation (APA) is a widespread posttranscriptional regulation process. APA generates diverse mRNA isoforms with different 3' UTR lengths, affecting mRNA expression, miRNA binding regulation and alternative splicing events. Previous studies have demonstrated the important roles of APA in tumorigenesis and cancer progression through diverse aspects. Thus, a comprehensive functional landscape of diverse APA events would aid in a better understanding of the underlying mechanisms related to APA in human cancers. Here, we built CAFuncAPA (https://relab.xidian.edu.cn/CAFuncAPA/) to systematically annotate the functions of 15478 APA events in human pan-cancers. Specifically, we first identified APA events associated with cancer survival and tumor progression. We annotated the potential downstream effects of APA on genes/isoforms expression, regulation of miRNAs, RNA binding proteins (RBPs) and alternative splicing events. Moreover, we also identified up-regulators of APA events, including the effects of genetic variants on poly(A) sites and RBPs, as well as the effect of methylation phenotypes on APA events. These findings suggested that CAFuncAPA can be a helpful resource for a better understanding of APA regulators and potential functions in cancer biology.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10671892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oncogenic ERRB2 signals through the AP-1 transcription factor to control mesenchymal-like properties of oesophageal adenocarcinoma. 致癌物质ERRB2通过AP-1转录因子发出信号，控制食管腺癌的间质样特性。

NAR Cancer Pub Date : 2023-01-23 eCollection Date: 2023-03-01 DOI: 10.1093/narcan/zcad001

Samuel Ogden, Ibrahim Ahmed, Shen-Hsi Yang, Paul Fullwood, Chiara Francavilla, Andrew D Sharrocks

{"title":"Oncogenic ERRB2 signals through the AP-1 transcription factor to control mesenchymal-like properties of oesophageal adenocarcinoma.","authors":"Samuel Ogden, Ibrahim Ahmed, Shen-Hsi Yang, Paul Fullwood, Chiara Francavilla, Andrew D Sharrocks","doi":"10.1093/narcan/zcad001","DOIUrl":"10.1093/narcan/zcad001","url":null,"abstract":"Oesophageal adenocarcinoma (OAC) is a deadly disease with poor survival statistics and few targeted therapies available. One of the most common molecular aberrations in OAC is amplification or activation of the gene encoding the receptor tyrosine kinase ERBB2, and ERBB2 is targeted in the clinic for this subset of patients. However, the downstream consequences of these ERBB2 activating events are not well understood. Here we used a combination of phosphoproteomics, open chromatin profiling and transcriptome analysis on cell line models and patient-derived datasets to interrogate the molecular pathways operating downstream from ERBB2. Integrated analysis of these data sets converge on a model where dysregulated ERBB2 signalling is mediated at the transcriptional level by the transcription factor AP-1. AP-1 in turn controls cell behaviour by acting on cohorts of genes that regulate cell migration and adhesion, features often associated with EMT. Our study therefore provides a valuable resource for the cancer cell signalling community and reveals novel molecular determinants underlying the dysregulated behaviour of OAC cells.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10255331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EEPD1 promotes repair of oxidatively-stressed replication forks. EEPD1促进氧化应激复制叉的修复。

NAR Cancer Pub Date : 2023-01-18 eCollection Date: 2023-03-01 DOI: 10.1093/narcan/zcac044

Aruna S Jaiswal, Hyun-Suk Kim, Orlando D Schärer, Neelam Sharma, Elizabeth A Williamson, Gayathri Srinivasan, Linda Phillips, Kimi Kong, Shailee Arya, Anurag Misra, Arijit Dutta, Yogesh Gupta, Christi A Walter, Sandeep Burma, Satya Narayan, Patrick Sung, Jac A Nickoloff, Robert Hromas

{"title":"EEPD1 promotes repair of oxidatively-stressed replication forks.","authors":"Aruna S Jaiswal, Hyun-Suk Kim, Orlando D Schärer, Neelam Sharma, Elizabeth A Williamson, Gayathri Srinivasan, Linda Phillips, Kimi Kong, Shailee Arya, Anurag Misra, Arijit Dutta, Yogesh Gupta, Christi A Walter, Sandeep Burma, Satya Narayan, Patrick Sung, Jac A Nickoloff, Robert Hromas","doi":"10.1093/narcan/zcac044","DOIUrl":"10.1093/narcan/zcac044","url":null,"abstract":"Unrepaired oxidatively-stressed replication forks can lead to chromosomal instability and neoplastic transformation or cell death. To meet these challenges cells have evolved a robust mechanism to repair oxidative genomic DNA damage through the base excision repair (BER) pathway, but less is known about repair of oxidative damage at replication forks. We found that depletion or genetic deletion of EEPD1 decreases clonogenic cell survival after oxidative DNA damage. We demonstrate that EEPD1 is recruited to replication forks stressed by oxidative damage induced by H2O2 and that EEPD1 promotes replication fork repair and restart and decreases chromosomal abnormalities after such damage. EEPD1 binds to abasic DNA structures and promotes resolution of genomic abasic sites after oxidative stress. We further observed that restoration of expression of EEPD1 via expression vector transfection restores cell survival and suppresses chromosomal abnormalities induced by oxidative stress in EEPD1-depleted cells. Consistent with this, we found that EEPD1 preserves replication fork integrity by preventing oxidatively-stressed unrepaired fork fusion, thereby decreasing chromosome instability and mitotic abnormalities. Our results indicate a novel role for EEPD1 in replication fork preservation and maintenance of chromosomal stability during oxidative stress.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9771122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Longitudinal evaluation of serum microRNAs as biomarkers for neuroblastoma burden and therapeutic p53 reactivation. 将血清微RNA作为神经母细胞瘤负担和治疗性p53再激活的生物标记物的纵向评估。

NAR Cancer Pub Date : 2023-01-18 eCollection Date: 2023-03-01 DOI: 10.1093/narcan/zcad002

Alan Van Goethem, Jill Deleu, Nurten Yigit, Celine Everaert, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Fjoralba Zeka, Fleur Demuynck, Eveline Barbieri, Frank Speleman, Pieter Mestdagh, Jason Shohet, Jo Vandesompele, Tom Van Maerken

{"title":"Longitudinal evaluation of serum microRNAs as biomarkers for neuroblastoma burden and therapeutic p53 reactivation.","authors":"Alan Van Goethem, Jill Deleu, Nurten Yigit, Celine Everaert, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Fjoralba Zeka, Fleur Demuynck, Eveline Barbieri, Frank Speleman, Pieter Mestdagh, Jason Shohet, Jo Vandesompele, Tom Van Maerken","doi":"10.1093/narcan/zcad002","DOIUrl":"10.1093/narcan/zcad002","url":null,"abstract":"Accurate assessment of treatment response and residual disease is indispensable for the evaluation of cancer treatment efficacy. However, performing tissue biopsies for longitudinal follow-up poses a major challenge in the management of solid tumours like neuroblastoma. In the present study, we evaluated whether circulating miRNAs are suitable to monitor neuroblastoma tumour burden and whether treatment-induced changes of miRNA abundance in the tumour are detectable in serum. We performed small RNA sequencing on longitudinally collected serum samples from mice carrying orthotopic neuroblastoma xenografts that were exposed to treatment with idasanutlin or temsirolimus. We identified 57 serum miRNAs to be differentially expressed upon xenograft tumour manifestation, out of which 21 were also found specifically expressed in the serum of human high-risk neuroblastoma patients. The murine serum levels of these 57 miRNAs correlated with tumour tissue expression and tumour volume, suggesting potential utility for monitoring tumour burden. In addition, we describe serum miRNAs that dynamically respond to p53 activation following treatment of engrafted mice with idasanutlin. We identified idasanutlin-induced serum miRNA expression changes upon one day and 11 days of treatment. By limiting to miRNAs with a tumour-related induction, we put forward hsa-miR-34a-5p as a potential pharmacodynamic biomarker of p53 activation in serum.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/21/zcad002.PMC9846426.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10635063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0