{"title":"Downregulation of circular RNA hsa_circ_0087856 sensitizes bladder cancer cells to cisplatin through targeting miR-1184/CITED2 signaling","authors":"Min Ju, Weiwei Wu, Jingkun Qu, Yang Sun, Jun Li","doi":"10.1002/em.22561","DOIUrl":"10.1002/em.22561","url":null,"abstract":"<p>CircRNAs are considered as one of the potential therapeutic targets of multiple cancers. According to accumulating evidence, circRNA regulates cancer progression by acting as a miRNA sponge. In the current work, our data discovered that hsa_circ_0087856 and CITED2 expression was increased, while miR-1184 expression was decreased in BC cell lines and tissues. Hsa_circ_0087856 expression negatively correlated with miR-1184, whereas positively correlated with CITED2. Hsa_circ_0087856 silencing suppressed BC tumor growth, and contributed to the inhibition of cisplatin to tumor growth. In cellular experiments, hsa_circ_0087856 increasing promoted BC cells proliferation, migration and invasion, and inhibited the cells apoptosis. Hsa_circ_0087856 increasing partly reversed the inhibition of cisplatin to BC cell proliferation and the promotion to cell apoptosis. Oppositely, hsa_circ_0087856 silencing could increase the sensitivity of BC cells to cisplatin. Hsa_circ_0087856 promoted CITED2 expression through binding with miR-1184 and inhibiting its expression. CITED2 increasing partly reversed the promotion of hsa_circ_0087856 silencing to cisplatin-induced BC cells apoptosis promotion and proliferation suppression. Overall, our results revealed the role of hsa_circ_0087856 that downregulation its expression could enhance the BC cells sensitivity to cisplatin by facilitating CITED expression via sponging miR-1184. Moreover, our research provided a potential therapeutic target for BC.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 6","pages":"342-353"},"PeriodicalIF":2.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9883532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Circ_0000033 up-regulates NUAK2 by sequestering miR-378a-3p to promote breast tumorigenesis","authors":"Yijun Dai, Wenjian Shi, Yanru Qiu, Tianwen Xu, Jianguang Lin, Yunxia Su","doi":"10.1002/em.22558","DOIUrl":"10.1002/em.22558","url":null,"abstract":"<p>Circular RNAs (circRNAs), including circ_0000033, were shown to be abnormally expressed in breast cancer (BC) and play an important regulatory function in the development of this cancer. This study aimed to investigate the action and mechanism of circ_0000033 in BC carcinogenesis. Specifically, levels of genes and proteins were analyzed using quantitative real-time PCR (qRT-PCR) and western blotting. Circ_0000033 was highly expressed in BC tissues and cells. Properties of cells with modified expression of circ_0000033 were characterized using an in vitro colony formation assay, EdU assay, flow cytometry, caspase-3 activity analysis, transwell assay, and tube formation assay, respectively. Functionally, knockdown of circ_0000033 suppressed BC cell proliferation, migration, invasion, angiogenesis, and induced apoptosis and cell cycle arrest in vitro. An in vivo experiment was conducted using a murine xenograft model and showed circ_0000033 silencing also impeded the growth of BC in nude mice. The binding between miR-378a-3p and circ_0000033 or NUAK2 (NUAK Family Kinase 2) was validated using a dual-luciferase reporter assay. Circ_0000033 sequestered miR-378a-3p and resulted in NUAK2 release, indicating a circ_0000033/miR-378a-3p/NUAK2 regulatory network operates in BC cells. Circ_0000033 down-regulation in BC cells was accompanied by decreased NUAK2 and increased miR-378a-3p expression. Moreover, the anticancer effects mediated by circ_0000033 knockdown were abolished by miR-378a-3p inhibition or NUAK2 overexpression in BC cells. Overall, circ_0000033 up-regulates NUAK2 through sequestration miR-378a-3p, which promoted breast tumorigenesis, suggesting circ_0000033 is a promising therapeutic target for BC treatment.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 6","pages":"359-370"},"PeriodicalIF":2.8,"publicationDate":"2023-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9883526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Associations between KCNQ1OT1 genetic variation rs10766212 and susceptibility to colorectal cancer and clinical stage in a Chinese Han population","authors":"Wanjia Nie, Shulong Zhang, Xueren Gao","doi":"10.1002/em.22559","DOIUrl":"10.1002/em.22559","url":null,"abstract":"<p>KCNQ1OT1 has been linked to the development and progression of colorectal cancer (CRC). As a result, functional polymorphisms in the <i>KCNQ1OT1</i> gene may have a role in CRC formation and progression. The goal of this study was to see if the rs10766212 polymorphism on the <i>KCNQ1OT1</i> gene was linked to CRC susceptibility and clinical stage in a Chinese Han population. The case–control research comprised a total of 576 CRC patients and 606 healthy controls. The genotype of the rs10766212 polymorphic locus was determined using the Sanger sequencing technique. We found that the <i>KCNQ1OT1</i> rs10766212 polymorphism was not related to CRC susceptibility; however, it was connected with the clinical stage of CRC. Patients with CRC who had the rs10766212 T allele had a lower risk of stage III/IV tumors than those who had the rs10766212 C allele. Furthermore, CRC tissues with the rs10766212 CC genotype showed a significant negative connection between KCNQ1OT1 and hsa-miR-622 expression. The luciferase assay showed that the rs10766212 C allele might contribute to the adsorption of KCNQ1OT1 on hsa-miR-622. In conclusion, the rs10766212 polymorphism altering hsa-miR-622 binding is linked to the clinical stage of CRC and may serve as a biomarker for predicting CRC progression in the Chinese Han population. However, better-designed studies are still needed to confirm the current findings.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 6","pages":"354-358"},"PeriodicalIF":2.8,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9957598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functional roles and cancer variants of the bifunctional glycosylase NEIL2","authors":"Anh B. Hua, Joann B. Sweasy","doi":"10.1002/em.22555","DOIUrl":"10.1002/em.22555","url":null,"abstract":"<p>Over 70,000 DNA lesions occur in the cell every day, and the inability to properly repair them can lead to mutations and destabilize the genome, resulting in carcinogenesis. The base excision repair (BER) pathway is critical for maintaining genomic integrity by repairing small base lesions, abasic sites and single-stranded breaks. Monofunctional and bifunctional glycosylases initiate the first step of BER by recognizing and excising specific base lesions, followed by DNA end processing, gap filling, and finally nick sealing. The Nei-like 2 (NEIL2) enzyme is a critical bifunctional DNA glycosylase in BER that preferentially excises cytosine oxidation products and abasic sites from single-stranded, double-stranded, and bubble-structured DNA. NEIL2 has been implicated to have important roles in several cellular functions, including genome maintenance, participation in active demethylation, and modulation of the immune response. Several germline and somatic variants of NEIL2 with altered expression and enzymatic activity have been reported in the literature linking them to cancers. In this review, we provide an overview of NEIL2 cellular functions and summarize current findings on NEIL2 variants and their relationship to cancer.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"65 S1","pages":"40-56"},"PeriodicalIF":2.8,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22555","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9676036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irina G. Minko, Andrew H. Kellum Jr., Michael P. Stone, R. Stephen Lloyd
{"title":"The aflatoxin B1-induced imidazole ring-opened guanine adduct: High mutagenic potential that is minimally affected by sequence context","authors":"Irina G. Minko, Andrew H. Kellum Jr., Michael P. Stone, R. Stephen Lloyd","doi":"10.1002/em.22556","DOIUrl":"10.1002/em.22556","url":null,"abstract":"<p>Dietary exposure to aflatoxin B<sub>1</sub> (AFB<sub>1</sub>) is a recognized risk factor for developing hepatocellular carcinoma. The mutational signature of AFB<sub>1</sub> is characterized by high-frequency base substitutions, predominantly G>T transversions, in a limited subset of trinucleotide sequences. The 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B<sub>1</sub> (AFB<sub>1</sub>-FapyGua) has been implicated as the primary DNA lesion responsible for AFB<sub>1</sub>-induced mutations. This study evaluated the mutagenic potential of AFB<sub>1</sub>-FapyGua in four sequence contexts, including hot- and cold-spot sequences as apparent in the mutational signature. Vectors containing site-specific AFB<sub>1</sub>-FapyGua lesions were replicated in primate cells and the products of replication were isolated and sequenced. Consistent with the role of AFB<sub>1</sub>-FapyGua in AFB<sub>1</sub>-induced mutagenesis, AFB<sub>1</sub>-FapyGua was highly mutagenic in all four sequence contexts, causing G>T transversions and other base substitutions at frequencies of ~80%–90%. These data suggest that the unique mutational signature of AFB<sub>1</sub> is not explained by sequence-dependent fidelity of replication past AFB<sub>1</sub>-FapyGua lesions.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"65 S1","pages":"9-13"},"PeriodicalIF":2.8,"publicationDate":"2023-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10711146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9683732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A scoping review of recent advances in the application of comet assay to Allium cepa roots","authors":"Carlotta Alias, Ilaria Zerbini, Donatella Feretti","doi":"10.1002/em.22553","DOIUrl":"10.1002/em.22553","url":null,"abstract":"<p>The comet assay is a sensitive method for the evaluation of DNA damages and DNA repair capacity at single-cell level. <i>Allium cepa</i> is a well-established plant model for toxicological studies. The aim of this scoping review was to investigate the recent application of the comet assay in <i>Allium cepa</i> root cells to assess the genotoxicity. To explore the literature a search was performed selecting articles published between January 2015 and February 2023 from Web of Science, PubMed, and Scopus databases using the combined search terms “Comet assay” and “<i>Allium cepa</i>”. All the original articles that applied the comet assay to <i>Allium cepa</i> root cells were included. Of the 334 records initially found, 79 articles were identified as meeting the inclusion criteria. Some studies reported results for two or more toxicants. In these cases, the data for each toxicant were treated separately. Thus, the number of analyzed toxicants (such as chemicals, new materials, and environmental matrices) was higher than the number of selected papers and reached 90. The current use of the <i>Allium</i>-comet assay seems to be directed towards two types of approach: the direct study of the genotoxicity of compounds, mainly biocides (20% of analyzed compounds) and nano- and microparticles (17%), and assessing a treatment's ability to reduce or eliminate genotoxicity of known genotoxicants (19%). Although the genotoxicity identified by the <i>Allium</i>-comet assay is only one piece of a larger puzzle, this method could be considered a useful tool for screening the genotoxic potential of compounds released into the environment.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 5","pages":"264-281"},"PeriodicalIF":2.8,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22553","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ASIP gene polymorphism associated with black coat and skin color in Murrah buffalo","authors":"Namita Kumari, Rashi Vasisth, Ankita Gurao, Manishi Mukesh, Vikas Vohra, Sanjay Kumar, Ranjit Singh Kataria","doi":"10.1002/em.22554","DOIUrl":"10.1002/em.22554","url":null,"abstract":"<p>The melanogenesis pathway regulates pigmentation through the synergic action of various genes. We are interested in analyzing the genetic variations in the ASIP which determine eumelanin production in the dermis layer. In the present study, the <i>ASIP</i> gene was characterized in buffalo and 268 genetically unrelated buffaloes belonging to 10 different populations were genotyped for the non-synonymous SNP (c.292C>T) identified in the exon 3 region of the gene using Tetra-ARMS-PCR. The TT genotype occurred at a higher rate in Murrah, followed by Nili Ravi, Tripura, and Paralakhemundi (42.63%, 19.30%, 3.45%, and 3.33%). These results convey the association of the black coat color of Murrah with the <i>ASIP</i> gene TT genotype and the lighter shades of black coat (brown and grayish-black) color phenotype in other breeds with the CC genotype.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 5","pages":"309-314"},"PeriodicalIF":2.8,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9732486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum to “Genotoxic repercussion of high-intensity radiation (x-rays) on hospital radiographers”","authors":"","doi":"10.1002/em.22542","DOIUrl":"10.1002/em.22542","url":null,"abstract":"<p>Kuchi Bhotla, H., Balasubramanian, B., Rengasamy, K.R.R., Arumugam, V.A., Alagamuthu, K.K., Chithravel, V. et al. (2023) Genotoxic repercussion of high-intensity radiation (x-rays) on hospital radiographers. <i>Environmental and Molecular Mutagenesis</i>, 64(2), 123–131.</p><p>In the original article the Ethics approval section has not been included. The Ethics approval section should read as follows:</p><p><b>ETHICS APPROVAL STATEMENT</b></p><p>The study was approved and got its ethical clearance from the Institutional committee from Christ University (Ethical Reference No. ECR/793/Inst/KA/2015/RR-18) and followed the protocols of ethical standards of Declaration of Helsinki 1964, WMA, 2000.</p><p>We apologize for this error.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 5","pages":"321"},"PeriodicalIF":2.8,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9658858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A study on Amygdalin's genotoxicological safety and modulatory activity in human peripheral lymphocytes in vitro","authors":"Esra Erikel, Deniz Yuzbasioglu, Fatma Unal","doi":"10.1002/em.22543","DOIUrl":"10.1002/em.22543","url":null,"abstract":"<p>Amygdalin (AMY), a plant secondary metabolite containing nitrile, is a major component of the seeds of Rosaceae family plants. It is known that this compound has many pharmacological activities such as cancer prevention, antipyretic, and cough suppressant. In this study, the genotoxic and modulatory effects of amygdalin were assessed by chromosomal aberration (CA), sister chromatid exchange (SCE), and cytokinesis-block micronucleus assay (CBMN) assays using human peripheral lymphocytes (HPLs) in the absence and presence of metabolic activator (S9 mix). Lymphocytes were exposed to various concentrations of amygdalin (0.86, 1.72, 3.43, 6.86, and 13.75 μg/mL) alone and in combination with mitomycin-C (MMC, 0.20 μg/mL) or cyclophosphamide (CP, 12 μg/mL). The mitotic index (MI), replication index (RI), cytokinesis-block proliferation index (CBPI), and cytostasis were also evaluated to determine cytotoxicity. Amygdalin alone did not exhibit genotoxic and cytotoxic effects at all the tested concentrations both in the absence and presence of the S9 mix. In contrast, amygdalin significantly reduced the frequencies of CA (especially at 48 h treatments), SCE, and MN (except 0.86 μg/mL in pre- and simultaneous treatment) induced by MMC in all the tested concentrations and treatment protocols. It has also considerably decreased CP-induced CA and SCE frequencies at all the concentrations (except 0.86 μg/mL) in simultaneous treatment. This study demonstrated that amygdalin alone was not genotoxic, on the contrary, it has revealed modulatory effects against chemotherapy agents that induced genomic damage in human lymphocytes, suggesting its chemopreventive potential.</p>","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 5","pages":"291-308"},"PeriodicalIF":2.8,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10034798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}