Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis最新文献

{"title":"The accurate bypass of pyrimidine dimers by DNA polymerase eta contributes to ultraviolet-induced mutagenesis","authors":"C.F.M. Menck ,&nbsp;R.S. Galhardo ,&nbsp;A. Quinet","doi":"10.1016/j.mrfmmm.2023.111840","DOIUrl":"10.1016/j.mrfmmm.2023.111840","url":null,"abstract":"<div><p><span>Human xeroderma pigmentosum variant (XP-V) patients are mutated in the </span><em>POLH</em><span><span> gene, responsible for encoding the translesion synthesis (TLS) DNA polymerase eta (Pol eta). These patients suffer from a high frequency of skin tumors. Despite several decades of research, studies on Pol eta still offer an intriguing paradox: How does this error-prone polymerase suppress mutations? This review examines recent evidence suggesting that cyclobutane pyrimidine dimers<span><span> (CPDs) are instructional for Pol eta. Consequently, it can accurately replicate these lesions, and the mutagenic effects induced by </span>UV radiation stem from the </span></span>deamination of C-containing CPDs. In this model, the deamination of C (forming a U) within CPDs leads to the correct insertion of an A opposite to the deaminated C (or U)-containing dimers. This intricate process results in C&gt;T transitions, which represent the most prevalent mutations detected in skin cancers. Finally, the delayed replication in XP-V cells amplifies the process of C-deamination in CPDs and increases the burden of C&gt;T mutations prevalent in XP-V tumors through the activity of backup TLS polymerases.</span></p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"828 ","pages":"Article 111840"},"PeriodicalIF":2.3,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135510545","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":"Downregulated CAV-1 in mouse spinal cord may alleviate bone cancer pain by inhibiting the ERK/CREB pathway","authors":"Jianyun Ge ,&nbsp;Jie Song ,&nbsp;Bo Sun ,&nbsp;Xuefeng Yang ,&nbsp;Boxiang Du ,&nbsp;Xin Sun ,&nbsp;Jiejie Zhang ,&nbsp;Jianlin Ge ,&nbsp;Hong Xie","doi":"10.1016/j.mrfmmm.2023.111829","DOIUrl":"10.1016/j.mrfmmm.2023.111829","url":null,"abstract":"<div><h3>Background</h3><p><span>This study aimed to assess the potential function of Caveolin-1 (CAV-1) in mice with bone cancer pain. Method: Using a mice bone cancer pain model we explored the contribution of CAV-1 expression to bone cancer pain on the 14th day after surgery, mice in the tumor group were randomized and treated with increasing doses of the CAV-1 inhibitor, methyl-beta-cyclodextrin. Pain was assessed by monitoring the number of spontaneous flinches (NSF) and paw withdrawal mechanical threshold (PMWT)mechanical withdrawal threshold (MWT). The localization and expression of CAV-1 in mouse neurons was also determined. Additionally, the protein levels of CAV-1, extracellular signal regulated kinase<span> (ERK) 1/2, cAMP response element-binding protein (CREB) were monitored in mouse spinal cord tissues by western blotting. Results: CAV-1 was remarkably upregulated in the spinal cord of the tumor group on the 4th day after surgery, then downregulated on day 10, and upregulated again at day 14. Such CAV-1 levels were maintained until day 28. In the tumor group, the expression of p-ERK1/2 and p-CERB were upregulated at day 14 after surgery. </span></span>Intrathecal injection of methyl-beta-cyclodextrin (MCD) downregulated p-ERK1/2 and p-CERB expression which correlated with alleviation of pain. Conclusion: Inhibition of CAV-1 in the spinal cord alleviates bone cancer pain in mice which correlates with inhibition of the ERK/CREB pathway.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"827 ","pages":"Article 111829"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9758250","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":"Oxidative and DNA damage in obese patients undergoing bariatric surgery: A one-year follow-up study","authors":"Anna Chiaramonte ,&nbsp;Serena Testi ,&nbsp;Caterina Pelosini ,&nbsp;Consuelo Micheli ,&nbsp;Aurora Falaschi ,&nbsp;Giovanni Ceccarini ,&nbsp;Ferruccio Santini ,&nbsp;Roberto Scarpato","doi":"10.1016/j.mrfmmm.2023.111827","DOIUrl":"10.1016/j.mrfmmm.2023.111827","url":null,"abstract":"<div><p>The pathogenesis of obesity and related comorbidities has long been associated with oxidative stress. The excess of adipose tissue contributes to the production of free radicals that sustain both a local and a systemic chronic inflammatory state, whereas its reduction can bring to an improvement in inflammation and oxidative stress. In our work, using the fluorescent lipid probe BODIPY® 581/591 C₁₁ and the γH2AX foci assay, a well-known marker of DNA double strand breaks (DSB), we evaluated the extent of cell membrane oxidation and DNA damage in peripheral blood lymphocytes of normal weight (NW) controls and obese patients sampled before and after bariatric surgery. Compared to NW controls, we observed a marked increase in both the frequencies of oxidized cells or nuclei exhibiting phosphorylation of histone H2AX in preoperatory obese patients. After bariatric surgery, obese patients, resampled over one-year follow-up, improved oxidative damage and reduced the presence of DSB. In conclusion, the present study highlights the importance for obese patients undergoing bariatric surgery to also monitor these molecular markers during their postoperative follow-up.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"827 ","pages":"Article 111827"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678582","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":"DinB (DNA polymerase IV), ImuBC and RpoS contribute to the generation of ciprofloxacin-resistance mutations in Pseudomonas aeruginosa","authors":"Declan Fahey ,&nbsp;James O’Brien ,&nbsp;Joanne Pagnon ,&nbsp;Simone Page ,&nbsp;Richard Wilson ,&nbsp;Nic Slamen ,&nbsp;Louise Roddam ,&nbsp;Mark Ambrose","doi":"10.1016/j.mrfmmm.2023.111836","DOIUrl":"10.1016/j.mrfmmm.2023.111836","url":null,"abstract":"<div><p>We investigated the role(s) of the damage-inducible SOS response <em>dinB</em> and <em>imuBC</em> gene products in the generation of ciprofloxacin-resistance mutations in the important human opportunistic bacterial pathogen, <em>Pseudomonas aeruginosa</em>. We found that the overall numbers of ciprofloxacin resistant (Cip^R) mutants able to be recovered under conditions of selection were significantly reduced when the bacterial cells concerned carried a defective <em>dinB</em> gene, but could be elevated to levels approaching wild-type when these cells were supplied with the <em>dinB</em> gene on a plasmid vector; in turn, firmly establishing a role for the <em>dinB</em> gene product, error-prone DNA polymerase IV, in the generation of Cip^R mutations in <em>P</em>. <em>aeruginosa</em>. Further, we report that products of the SOS-regulated <em>imuABC</em> gene cassette of this organism, ImuB and the error-prone ImuC DNA polymerase, are also involved in generating Cip^R mutations in this organism, since the yields of Cip^R mutations were substantially decreased in <em>imuB</em>- or <em>imuC</em>-defective cells compared to wild-type. Intriguingly, we found that the mutability of a <em>dinB</em>-defective strain could not be rescued by overexpression of the <em>imuBC</em> genes. And similarly, overexpression of the <em>dinB</em> gene either only modestly or else failed to restore Cip^R mutations in <em>imuB</em>- or <em>imuC</em>-defective cells, respectively. Combined, these results indicated that the products of the <em>dinB</em> and <em>imuBC</em> genes were acting in the same pathway leading to the generation of Cip^R mutations in <em>P</em>. <em>aeruginosa</em>. In addition, we provide evidence indicating that the general stress response sigma factor σ^s, RpoS, is required for mutagenesis in this organism and is in part at least modulating the <em>dinB</em> (DNA polymerase IV)-dependent mutational process. Altogether, these data provide further insight into the complexity and multifaceted control of the mutational mechanism(s) contributing to the generation of ciprofloxacin-resistance mutations in <em>P</em>. <em>aeruginosa</em>.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"827 ","pages":"Article 111836"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10070300","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":"Uncommon variants detected via hereditary cancer panel and suggestions for genetic counseling","authors":"Zeynep Özdemir ,&nbsp;Ezgi Çevik ,&nbsp;Ömür Berna Çakmak Öksüzoğlu ,&nbsp;Mutlu Doğan ,&nbsp;Öztürk Ateş ,&nbsp;Ece Esin ,&nbsp;İrem Bilgetekin ,&nbsp;Umut Demirci ,&nbsp;Çağlar Köseoğlu ,&nbsp;Alper Topal ,&nbsp;Nuri Karadurmuş ,&nbsp;Haktan Bağış Erdem ,&nbsp;Taha Bahsi","doi":"10.1016/j.mrfmmm.2023.111831","DOIUrl":"10.1016/j.mrfmmm.2023.111831","url":null,"abstract":"<div><h3>Objective</h3><p>Hereditary cancer syndromes<span> constitute 5–10% of all cancers. The development of next-generation sequencing technologies has made it possible to examine many hereditary cancer syndrome-causing genes in a single panel. This study's goal was to describe the prevalence and the variant spectrum using NGS in individuals who were thought to have a hereditary predisposition for cancer.</span></p></div><div><h3>Material and method</h3><p>Analysis was performed for 1254 who were thought to have a familial predisposition for cancer. We excluded 46 patients who were carrying <em>BRCA1/2</em><span><span> variants in this study, for focusing on the rare gene mutations. Sequencing was performed using the </span>Sophia<span> Hereditary Cancer Solution v1.1 Panel and the Qiagen Large Hereditary Cancer Panel. The Illumina MiSeq system was used for the sequencing procedure. The software used for the data analyses was Sophia DDM and QIAGEN Clinical Insight (QCITM) Analyze. The resulting genomic changes were classified according to the current guidelines of ACMG/AMP.</span></span></p></div><div><h3>Results</h3><p>Pathogenic/likely pathogenic variants were detected in 172 (13.7%) of 1254 patients. After excluding the 46 <em>BRCA1/2</em><span><span><span>-positive patients, among the remaining 126 patients; there were 60 (4.8%) breast cancer, 33 (2.6%) colorectal cancer, 9 (0.7%) </span>ovarian cancer<span>, 5 (0.4%) endometrium cancer, 5 (0.4%) stomach cancer, 3 (0.2%) </span></span>prostate cancer patients. The most altered genes were </span><span><em>MUTYH</em></span> in 27 (2.1%) patients, MMR genes (<span><span><span><span><em>MLH1</em><em>, </em></span><em>MSH6</em><em>, </em></span><em>MSH</em><span><em>, </em><em>MSH2</em><em>, </em></span></span><em>PMS2</em><em> and EPCAM</em></span>) in 26 (2%) patients, and <em>ATM</em> in 25 (2%) patients. We also examined the genotype-phenotype correlation in rare variants. Additionally, we identified 11 novel variations.</p></div><div><h3>Conclusion</h3><p>This study provided significant information regarding rare variants observed in the Turkish population because it was carried out with a large patient group. Personalized treatment options and genetic counseling for the patients are therefore made facilitated.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"827 ","pages":"Article 111831"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9769666","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":"Lethal and mutagenic effects of different LET radiations on Bacillus subtilis spores","authors":"Katsuya Satoh ,&nbsp;Wataru Hoshino ,&nbsp;Yoshihiro Hase ,&nbsp;Satoshi Kitamura ,&nbsp;Hidenori Hayashi ,&nbsp;Masakazu Furuta ,&nbsp;Yutaka Oono","doi":"10.1016/j.mrfmmm.2023.111835","DOIUrl":"10.1016/j.mrfmmm.2023.111835","url":null,"abstract":"<div><p><span>New, useful microorganism<span> resources have been generated by ionizing radiation<span><span> breeding technology<span>. However, the mutagenic effects of ionizing radiation on microorganisms have not been systematically clarified. For a deeper understanding and characterization of ionizing radiation-induced mutations in microorganisms, we investigated the lethal effects of seven different </span></span>linear energy transfer (LET) radiations based on the survival fraction (SF) and whole-genome sequencing analysis of the mutagenic effects of a dose resulting in an SF of around 1% in </span></span></span><em>Bacillus subtilis</em> spores. Consequently, the lower LET radiations (gamma [surface LET: 0.2 keV/µm] and ⁴He²⁺<span><span> [24 keV/µm]) showed low lethality and high </span>mutation frequency (MF), resulting in the major induction of single-base substitutions. Whereas higher LET radiations (</span>¹²C⁵⁺ [156 keV/µm] and ¹²C⁶⁺ [179 keV/µm]) showed high lethality and low MF, resulting in the preferential induction of deletion mutations. In addition, ¹²C⁶⁺<span><span> (111) ion beams likely possess characteristics of both low- and high-LET radiations simultaneously. A decrease in the </span>relative biological effectiveness and an evaluation of the inactivation cross section indicated that </span>²⁰Ne⁸⁺ (468 keV/µm) and ⁴⁰Ar¹³⁺<span> (2214 keV/µm) ion beams had overkill effects. In conclusion, in the mutation breeding of microorganisms, it should be possible to regulate the proportions, types, and frequencies of induced mutations by selecting an ionizing radiation of an appropriate LET in accordance with the intended purpose.</span></p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"827 ","pages":"Article 111835"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9971357","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":"The E2F1/MELTF axis fosters the progression of lung adenocarcinoma by regulating the Notch signaling pathway","authors":"Lidan Zhang,&nbsp;Lei Shi","doi":"10.1016/j.mrfmmm.2023.111837","DOIUrl":"10.1016/j.mrfmmm.2023.111837","url":null,"abstract":"<div><h3>Background</h3><p><span>Lung adenocarcinoma (LUAD) represents the predominant subtype of lung cancer. MELTF, an </span>oncogene, exhibits high expression in various cancer tissues. Nevertheless, the precise role of MELTF in the progression of LUAD remains enigmatic. This work was devised to investigate the effect of MELTF on LUAD progression and its underlying mechanism.</p></div><div><h3>Methods</h3><p><span>mRNA expression data of LUAD were from The Cancer Genome Atlas database, and the enrichment pathway of MELTF was analyzed. The upstream transcription factors<span> of MELTF were predicted, and the correlation between MELTF and E2F1 as well as the expression of the two in LUAD tissues were dissected by bioinformatics. The expression of MELTF and E2F1 in LUAD tissues and cells was assayed by qRT-PCR. Effects of MELTF/E2F1 on proliferation, migration, and invasion of LUAD cells were tested by CCK-8, colony formation, and Transwell assays. The binding relationship between E2F1 and MELTF was estimated by dual-luciferase reporter gene assay and </span></span>ChIP<span> assay. Western blot was utilized to assay the expression of Notch signaling pathway-related proteins in different treatment groups.</span></p></div><div><h3>Results</h3><p><span>Bioinformatics analysis and qRT-PCR results exhibited high expression of E2F1 and MELTF in LUAD tissues and cells, respectively. Dual-luciferase reporter gene assay and ChIP assay ascertained the binding of E2F1 to MELTF. MELTF was ascertained to enrich the Notch signaling pathway<span> by bioinformatics means. In cell experiments, MELTF was shown to foster the malignant progression of LUAD cells and promoted the expression of NOTCH1 and HES1 proteins, but </span></span>RO4929097 offset the effect of MELTF on cells. Rescue assay confirmed that E2F1 activated MELTF to promote LUAD progression via the Notch signaling pathway.</p></div><div><h3>Conclusion</h3><p>Together, our outcomes demonstrated that E2F1 fostered LUAD progression by activating MELTF via the Notch signaling activity. Hence, MELTF emerged as a feasible target for treating LUAD.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"827 ","pages":"Article 111837"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224236","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":"Analysis of chemical structures and mutations detected by Salmonella TA98 and TA100","authors":"Kevin P. Cross ,&nbsp;David M. DeMarini","doi":"10.1016/j.mrfmmm.2023.111838","DOIUrl":"10.1016/j.mrfmmm.2023.111838","url":null,"abstract":"<div><p><span>As part of an analysis performed under the auspices of the International Workshop on Genotoxicity Testing (IWGT) in 2017, we and others showed that </span><em>Salmonella</em><span><span> frameshift strain TA98 and base-substitution strain TA100 together + /- S9 detected 93% of the mutagens<span> detected by all the bacterial strains recommended by OECD TG471 (Williams et al., Mutation Res. 848:503081, 2019). We have extended this analysis by identifying the numbers and chemical classes of chemicals detected by these two strains either alone or in combination, including the role of S9. Using the Leadscope 2021 SAR Genetox database containing &gt; 21,900 compounds, our dataset containing 7170 compounds tested in both TA98 and TA100. Together, TA98 and TA100 detected 94% (3733/3981) of the mutagens detected using all the TG471-recommended bacterial strains; 39% were mutagenic in one or both strains. TA100 detected 77% of all of these mutagens and TA98 70%. Considering the overlap of detection by both strains, 12% of these mutagens were detected only by TA98 and 19% only by TA100. In the absence of S9, sensitivity dropped by 31% for TA98 and 29% for TA100. Overall, 32% of the mutagens required S9 for detection by either strain; 9% were detected only without S9. Using the 2021 Leadscope Genetox Expert Alerts, TA100 detected 18 mutagenic alerting chemical classes with better sensitivity than TA98, whereas TA98 detected 10 classes better than TA100. TA100 detected more chemical classes than did TA98, especially </span></span>hydrazines<span><span><span><span>, azides, various di- and tri-halides, various </span>nitrosamines<span>, epoxides<span>, aziridines, difurans, and half-mustards; TA98 especially detected polycyclic primary amines, various </span></span></span>aromatic amines<span>, polycyclic aromatic hydrocarbons, triazines, and dibenzo-furans. Model compounds with these structures induce primarily G to T mutations in TA100 and/or a hotspot GC deletion in TA98. Both TA98 and TA100 + /- S9 are needed for adequate </span></span>mutagenicity screening with the </span></span><em>Salmonella</em> (Ames) assay.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"827 ","pages":"Article 111838"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125372","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":"LncRNA UCA1 could regulate the progression of neuropathic pain by regulating miR-135a-5p","authors":"Bingbing Wu,&nbsp;Xiaogang Zhou","doi":"10.1016/j.mrfmmm.2023.111833","DOIUrl":"10.1016/j.mrfmmm.2023.111833","url":null,"abstract":"<div><h3>Background</h3><p>Neuropathic pain<span><span> (NPP) is known as a common neurological disease with high incidence rate. The present work focused on the roles of long non-coding RNA </span>urothelial carcinoma antigen 1(LncRNA UCA1) in NPP and the possible underlying mechanism.</span></p></div><div><h3>Methods</h3><p>NPP rat model has been established and the levels of UCA1 NPP as well as the group has been determined by RT-PCR method. Next, NPP rats were treated by UCA1 over-expression plasmid and the behaviors, as well as expression of inflammatory cytokines have been examined. Furthermore, target miRNA of UCA1, miR-135a-5p, has been predicted by bioinformatic method, and further verified with the dual-luciferase reporter assay. Finally, the effects of UCA1/ miR-135a-5p axis have been further evaluated.</p></div><div><h3>Results</h3><p>Expressions of UCA1 were markedly decreased and miR-135a-5p were significantly increased in NPP rats in comparison with the control rats. Over-expression of UCA1 alleviated the inflammatory condition in NPP model by decreasing expression of inflammatory cytokines. miR-135a-5p was confirmed to be a target microRNA of UCA1, and UCA1 may regulate the progress of NPP via targeting miR-135a-5p.</p></div><div><h3>Conclusion</h3><p>UCA1 could regulate NPP via affecting miR-135a-5p expression.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"827 ","pages":"Article 111833"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10210898","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":"Hsa-miR-1269a up-regulation fosters the malignant progression of esophageal squamous cell carcinoma via targeting FAM46C","authors":"Yuefeng Ma ,&nbsp;Xin Xing ,&nbsp;Chuantao Cheng ,&nbsp;Ranran Kong ,&nbsp;Liangzhang Sun ,&nbsp;Feng Zhao ,&nbsp;Danjie Zhang ,&nbsp;Jianzhong Li","doi":"10.1016/j.mrfmmm.2023.111832","DOIUrl":"10.1016/j.mrfmmm.2023.111832","url":null,"abstract":"<div><p>Esophageal squamous cell carcinoma<span> (ESCC) is a malignancy of the alimentary tract resulting in death worldwide. The role and underlying mechanism of hsa-miR-1269a in the progression of ESCC remain unclear. In this study, hsa-miR-1269a was screened by differential expression analysis in TCGA, and its target gene FAM46C was predicted. qRT-PCR was conducted to assay the expression of hsa-miR-1269a and FAM46C in ESCC cells. The results showed that hsa-miR-1269a was upregulated in ESCC tissues and cell lines. Hsa-miR-1269a overexpression stimulated the proliferation, migration, and invasion capacities of ESCC cells, and FAM46C overexpression inhibited these phenotypes. Dual-luciferase assay verified that hsa-miR-1269a could target FAM46C. Next, qRT-PCR and western blot demonstrated that hsa-miR-1269a overexpression downregulated FAM46C. Rescue experiments revealed that hsa-miR-1269a accelerated the malignant progression of ESCC through FAM46C down-regulation. These results indicate that the interaction between hsa-miR-1269a and FAM46C plays a regulatory role in driving the malignant progression of ESCC cells, thereby providing a novel molecular mechanism for understanding ESCC.</span></p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"827 ","pages":"Article 111832"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828240","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}