Pub Date : 2022-07-01DOI: 10.1016/j.mrfmmm.2022.111796
Adriani Paganini Damiani, Marina Lummertz Magenis, Ligia Salvan Dagostin, Ângela Caroline da Luz Beretta, Rovena Jacobsen Sarter, Luiza Martins Longaretti, Isadora de Oliveira Monteiro, Vanessa Moraes de Andrade
Royal jelly (RJ) is a creamy white-yellow liquid that is secreted by the mandibular and hypopharyngeal glands of bees to nourish the larvae. RJ has gained increasing interest in recent years owing to its antioxidant potential. However, little is known about adequate RJ dosing and its effects on genetic material. Thus, the aim of this study was to evaluate the in vivo effects of RJ on genotoxicity and mutagenicity induced by the alkylating agent methyl methanesulfonate (MMS). In this study, 3-month-old Swiss albino male mice (N = 66) were divided into 11 groups for experimentation. Experiments were performed by administering lyophilized RJ (150 mg/kg, 300 mg/kg, and 1000 mg/kg) or water via gavage as pre- and posttreatment processes with the alkylating agent MMS. After treatment, blood samples were collected from the mice via an incision at the end of the tail to conduct comet assays at times of 24 h and 48 h posttreatment. The mice were then euthanized to remove the bone marrow for a micronucleus test. Overall, regardless of dose, RJ did not exhibit genotoxic, mutagenic activity and the administration of high doses, mainly in the form of posttreatment, presented antigenotoxic and antimutagenic actions. Further, a dose-response correlation was observed in the RJ posttreatment groups. These results demonstrate that RJ administration was effective in reversing the damage caused by the alkylating agent MMS.
{"title":"Royal jelly reduce DNA damage induced by alkylating agent in mice","authors":"Adriani Paganini Damiani, Marina Lummertz Magenis, Ligia Salvan Dagostin, Ângela Caroline da Luz Beretta, Rovena Jacobsen Sarter, Luiza Martins Longaretti, Isadora de Oliveira Monteiro, Vanessa Moraes de Andrade","doi":"10.1016/j.mrfmmm.2022.111796","DOIUrl":"10.1016/j.mrfmmm.2022.111796","url":null,"abstract":"<div><p><span><span>Royal jelly (RJ) is a creamy white-yellow liquid that is secreted by the mandibular and hypopharyngeal glands of bees to nourish the larvae. RJ has gained increasing interest in recent years owing to its antioxidant potential. However, little is known about adequate RJ dosing and its effects on genetic<span><span> material. Thus, the aim of this study was to evaluate the in vivo effects of RJ on genotoxicity and </span>mutagenicity induced by the </span></span>alkylating agent </span>methyl methanesulfonate<span><span> (MMS). In this study, 3-month-old Swiss albino male mice (N = 66) were divided into 11 groups for experimentation. Experiments were performed by administering lyophilized RJ (150 mg/kg, 300 mg/kg, and 1000 mg/kg) or water via gavage as pre- and posttreatment processes with the alkylating agent MMS. After treatment, blood samples were collected from the mice via an incision at the end of the tail to conduct </span>comet assays<span> at times of 24 h and 48 h posttreatment. The mice were then euthanized to remove the bone marrow for a micronucleus test<span>. Overall, regardless of dose, RJ did not exhibit genotoxic, mutagenic activity and the administration of high doses, mainly in the form of posttreatment, presented antigenotoxic and antimutagenic actions. Further, a dose-response correlation was observed in the RJ posttreatment groups. These results demonstrate that RJ administration was effective in reversing the damage caused by the alkylating agent MMS.</span></span></span></p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111796"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10351728","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}
Pub Date : 2022-07-01DOI: 10.1016/j.mrfmmm.2022.111795
Xiaoling Zhu , Jianfang Wang , Xueying Jin , Yiyi Chen , Liang Hu , Jianguo Zhao
In this study, mRNA expression of gastric cancer tissue and clinical data of patients in TCGA-STAD dataset were used, together with the hypoxia-related gene sets in the MsigDB database, to screen hypoxia-related differentially expressed genes (DEGs) in GC. Thereafter, univariate and multivariate Cox regression analyses were carried out on hypoxia-related DEGs. The optimal feature genes related to prognosis were obtained to construct a prognostic risk assessment model. According to the model, the riskScore of GC patients was measured, and GC samples were assigned into high- and low-risk groups in accordance with the median riskScore. Based on the Kaplan-Meier curve and Receiver operating characteristic curve, validity of the prognostic risk assessment model was measured. Gene set enrichment analysis was performed on the two risk groups through Gene set enrichment analysis software. The results revealed that in the high-risk group, 9 signaling pathways were remarkably activated in several terms, like focal adhesion, extracellular matrix receptor interaction, Cell adhesion molecules cams, Cytokine-cytokine receptor interaction, TGF-beta signaling pathway, NOD-like receptor signaling pathway, JAK-STAT signaling pathway, Toll-like receptor signaling pathway and MAPK signaling pathway. In combination with riskScore and clinical factors, univariate and multivariate Cox regression analyses verified the independence of the model. Meanwhile, a nomogram was constructed to predict the 1-, 3- and 5-year survival of GC patients. The calibration curve indicated that the survival status predicted by the nomogram fitted better with actual survival status. On the whole, the prognostic risk model of GC on the basis of hypoxia-related genes demonstrated good predictive ability. It can provide more powerful technical support for clinicians to make prognostic determination and therapeutic plans.
{"title":"Construction and evaluation of a prognostic risk assessment model of gastric cancer by using hypoxia features","authors":"Xiaoling Zhu , Jianfang Wang , Xueying Jin , Yiyi Chen , Liang Hu , Jianguo Zhao","doi":"10.1016/j.mrfmmm.2022.111795","DOIUrl":"10.1016/j.mrfmmm.2022.111795","url":null,"abstract":"<div><p><span>In this study, mRNA expression of gastric cancer tissue and clinical data of patients in TCGA-STAD dataset were used, together with the hypoxia-related gene sets in the MsigDB database, to screen hypoxia-related differentially expressed genes (DEGs) in GC. Thereafter, univariate and multivariate Cox regression analyses were carried out on hypoxia-related DEGs. The optimal feature genes related to prognosis were obtained to construct a prognostic risk assessment model. According to the model, the riskScore of GC patients was measured, and GC samples were assigned into high- and low-risk groups in accordance with the median riskScore. Based on the Kaplan-Meier curve and Receiver operating characteristic curve, validity of the prognostic risk assessment model was measured. Gene set enrichment analysis was performed on the two risk groups through Gene set enrichment analysis software. The results revealed that in the high-risk group, 9 </span>signaling pathways<span><span> were remarkably activated in several terms, like focal adhesion, extracellular matrix receptor interaction, </span>Cell adhesion molecules cams, Cytokine-cytokine receptor interaction, TGF-beta signaling pathway, NOD-like receptor signaling pathway, JAK-STAT signaling pathway, Toll-like receptor signaling pathway and MAPK signaling pathway. In combination with riskScore and clinical factors, univariate and multivariate Cox regression analyses verified the independence of the model. Meanwhile, a nomogram was constructed to predict the 1-, 3- and 5-year survival of GC patients. The calibration curve indicated that the survival status predicted by the nomogram fitted better with actual survival status. On the whole, the prognostic risk model of GC on the basis of hypoxia-related genes demonstrated good predictive ability. It can provide more powerful technical support for clinicians to make prognostic determination and therapeutic plans.</span></p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111795"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10351734","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}
Pub Date : 2022-07-01DOI: 10.1016/j.mrfmmm.2022.111797
Divyalakshmi Saini , Vinay Jain , Birajalaxmi Das
The high level natural radiation areas (HLNRA) of Kerala coast provide unique opportunity to study the biological effect of chronic low dose ionizing radiation (LDIR) on human population below 100 mSv. The radiation level in this area varies from < 1.0–45 mGy /year due to patchy distribution of monazite in the sand, which contains 232Th (8–10%), 238U (0.3%), and their decay products. Telomere length attrition has been correlated to DNA damage due to genotoxic agents. The objective of the present study is to evaluate the effect of natural chronic LDIR exposure on telomere length and transcriptional response of telomere specific and DNA damage repair genes in peripheral blood mononuclear cells (PBMCs) of individuals from normal level natural radiation areas (NLNRA) and HLNRA of Kerala coast, southwest India. Blood samples were collected from 71 random male donors (24–80 years) from NLNRA (≤1.50 mGy/year; N = 19) and two HLNRA dose groups [1.51–10 mGy/year (N = 17); > 10 mGy/year, (N = 35)]. Genomic DNA was isolated from PBMCs and relative telomere length (RTL) was determined using real time q-PCR. Radio-adaptive response (RAR) study was carried out in PBMCs of 40 random males from NLNRA (N = 20) and HLNRA (>10 mGy/year; N = 20), where PBMCs were given a challenged dose of 2.0 Gy gamma radiation at 4 h. Transcriptional profile of telomere specific (TRF1, TRF2, POT1, TIN2, TPP1, RAP1), DNA damage response (RAD17, ATM, CHEK1) and base excision repair pathway (BER) (OGG1, XRCC1, NTH1, NEIL1, MUTYH, MBD4) genes were analysed at basal level and after a challenge dose of 2.0 Gy at 4 h. Our results did not show any significant effect of chronic LDR on RTL among the individuals from NLNRA and two HLNRA groups (p = 0.195). However, influence of age on RTL was clearly evident among NLNRA and HLNRA individuals. At basal level, TRF1, TRF2, TIN2, MBD4, NEIL1 and RAD17 showed significant up-regulation, whereas XRCC1 was significantly down regulated in HLNRA individuals. After a challenge dose of 2.0 Gy, significant transcriptional up-regulation was observed at telomere specific (TRF2, POT1) and BER (MBD4, NEIL1) genes in HLNRA individuals as compared to NLNRA suggesting their role in RAR. In conclusion, elevated level of natural chronic LDR exposure did not have any adverse effect on telomere length in Kerala coast. Significant transcriptional response at TRF2, MBD4 and NEIL1 at basal level and with a challenge dose of 2.0 Gy sug
{"title":"Evaluation of natural chronic low dose radiation exposure on telomere length and transcriptional response of shelterin complex in individuals residing in Kerala coast, India","authors":"Divyalakshmi Saini , Vinay Jain , Birajalaxmi Das","doi":"10.1016/j.mrfmmm.2022.111797","DOIUrl":"10.1016/j.mrfmmm.2022.111797","url":null,"abstract":"<div><p><span><span>The high level natural radiation areas (HLNRA) of Kerala coast provide unique opportunity to study the biological effect of chronic low dose ionizing radiation (LDIR) on human population below 100 mSv. The radiation level in this area varies from < 1.0–45 mGy /year due to patchy distribution of </span>monazite in the sand, which contains </span><sup>232</sup>Th (8–10%), <sup>238</sup><span>U (0.3%), and their decay products. Telomere length<span><span><span> attrition has been correlated to DNA damage due to genotoxic agents. The objective of the present study is to evaluate the effect of natural chronic LDIR exposure on </span>telomere<span> length and transcriptional response of telomere specific and DNA damage repair genes in peripheral blood mononuclear cells (PBMCs) of individuals from normal level natural radiation areas (NLNRA) and HLNRA of Kerala coast, southwest India. Blood samples were collected from 71 random male donors (24–80 years) from NLNRA (≤1.50 mGy/year; N = 19) and two HLNRA dose groups [1.51–10 mGy/year (N = 17); > 10 mGy/year, (N = 35)]. Genomic DNA was isolated from PBMCs and relative telomere length (RTL) was determined using real time q-PCR. Radio-adaptive response (RAR) study was carried out in PBMCs of 40 random males from NLNRA (N = 20) and HLNRA (>10 mGy/year; N = 20), where PBMCs were given a challenged dose of 2.0 Gy </span></span>gamma radiation at 4 h. Transcriptional profile of telomere specific (</span></span><span><span><em>TRF1</em><span><em>, </em><em>TRF2</em><em>, POT1, </em></span></span><em>TIN2</em><span><em>, TPP1, </em><em>RAP1</em></span></span><span>), DNA damage response (</span><span><em>RAD17</em><span><em>, </em><em>ATM</em><em>, CHEK1)</em></span></span><span> and base excision repair pathway </span><span><em>(BER) (OGG1, </em><em>XRCC1</em><span><em>, NTH1, </em><em>NEIL1</em><span><em>, </em><em>MUTYH</em><em>, MBD4)</em></span></span></span> genes were analysed at basal level and after a challenge dose of 2.0 Gy at 4 h. Our results did not show any significant effect of chronic LDR on RTL among the individuals from NLNRA and two HLNRA groups (p = 0.195). However, influence of age on RTL was clearly evident among NLNRA and HLNRA individuals. At basal level, <span><em>TRF1, TRF2, TIN2, </em><em>MBD4</em></span>, <em>NEIL1</em> and <em>RAD17</em> showed significant up-regulation, whereas <em>XRCC1</em> was significantly down regulated in HLNRA individuals. After a challenge dose of 2.0 Gy, significant transcriptional up-regulation was observed at telomere specific (<em>TRF2</em>, <em>POT1)</em> and BER (<em>MBD4, NEIL1)</em> genes in HLNRA individuals as compared to NLNRA suggesting their role in RAR. In conclusion, elevated level of natural chronic LDR exposure did not have any adverse effect on telomere length in Kerala coast. Significant transcriptional response at <em>TRF2, MBD4</em> and <em>NEIL1</em><span> at basal level and with a challenge dose of 2.0 Gy sug","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111797"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10365183","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}
Pub Date : 2022-07-01DOI: 10.1016/j.mrfmmm.2022.111801
Daliang Kong , Yang Liu , Minglei Zhang
Purpose
The study objects were to explore the correlation between the biological role of clock genes and clinical indicators in patients with osteosarcoma (OS).
Methods
We acquired the clinical information and RNA sequencing data of OS samples from the TARGET database. The protein-protein interaction (PPI) network and expression correlation analysis of clock genes were performed. Then, the functional enrichment analysis of clock genes was analyzed. The survival analysis of clock genes in patients of OS was carried out by univariate cox regression, Kaplan-Meier (KM) curve and multivariate cox regression methods. Moreover, the spearmen correlation analysis was performed to explore the correlation between clock genes and DNA repair genes in patients with OS.
Results
The PPI network and expression correlation analysis of clock genes indicated that the clock genes were highly correlated with each other. The survival analysis of clock genes found that clock gene ARNTL is a protective factor for the prognosis of patients with OS. We found that ARNTL was positively related to DNA repair genes and was involved in the biological process of DNA damage repair in patients with OS.
Conclusions
ARNTL may affect the prognosis and chemotherapy response of patients with OS by regulating DNA repair pathways.
{"title":"Expression of the Circadian Clock Gene ARNTL associated with DNA repair gene and prognosis of patient with osteosarcoma","authors":"Daliang Kong , Yang Liu , Minglei Zhang","doi":"10.1016/j.mrfmmm.2022.111801","DOIUrl":"10.1016/j.mrfmmm.2022.111801","url":null,"abstract":"<div><h3>Purpose</h3><p>The study objects were to explore the correlation between the biological role of clock genes and clinical indicators in patients with osteosarcoma (OS).</p></div><div><h3>Methods</h3><p>We acquired the clinical information and RNA sequencing data of OS samples from the TARGET database. The protein-protein interaction (PPI) network and expression correlation analysis of clock genes were performed. Then, the functional enrichment analysis of clock genes was analyzed. The survival analysis of clock genes in patients of OS was carried out by univariate cox regression, Kaplan-Meier (KM) curve and multivariate cox regression methods. Moreover, the spearmen correlation analysis was performed to explore the correlation between clock genes and DNA repair genes in patients with OS.</p></div><div><h3>Results</h3><p>The PPI network and expression correlation analysis of clock genes indicated that the clock genes were highly correlated with each other. The survival analysis of clock genes found that clock gene ARNTL is a protective factor for the prognosis of patients with OS. We found that ARNTL was positively related to DNA repair genes and was involved in the biological process of DNA damage repair in patients with OS.</p></div><div><h3>Conclusions</h3><p>ARNTL may affect the prognosis and chemotherapy response of patients with OS by regulating DNA repair pathways.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111801"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0027510722000288/pdfft?md5=13f06852b07c7c6e96e107eb436d3a72&pid=1-s2.0-S0027510722000288-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10352278","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}
This study attempted to investigate the mechanism of miR-204-5p and its downstream gene in regulating bio-functions of esophageal cancer (EC).
Methods
Bioinformatics analysis was performed to select the mature miRNAs, mRNAs, and clinical data of EC. The miRNA-mRNA regulatory axis was predicted through bioinformatics and used Dual-luciferase analysis to verify the interaction between miR-204-5p and APLN. qRT-PCR was applied to analyze expression of miR-204-5p and APLN mRNA. Western blot was utilized to detect APLN protein expression. Functional assays like CCK-8, wound healing, Transwell, and stem cell sphere formation assays were launched to confirm proliferative, migratory, invasive and stemness of cells in different treatment groups.
Results
MiR-204-5p was lowly expressed while its target gene APLN was highly expressed in tumor tissues. Besides, miR-204-5p overexpression hindered proliferation, invasion, migration, and stemness of EC cells. Additionally, dual-luciferase assay verified the interaction of miR-204-5p and APLN. MiR-204-5p could downregulate APLN level and its overexpression reduced the effect of APLN on EC cell functions.
Conclusion
Dysregulation of miR-204-5p/APLN axis was linked with malignant progression of EC. MiR-204-5p/APLN may be an underlying candidate for the design of anticarcinogens.
{"title":"Dysregulation of miR-204-5p/APLN axis affects malignant progression and cell stemness of esophageal cancer","authors":"Yifan Zhou, Ruihong Xu, Jinlong Luo, Xiangwei Li, Yonglong Zhong, Zhendong Sun","doi":"10.1016/j.mrfmmm.2022.111791","DOIUrl":"10.1016/j.mrfmmm.2022.111791","url":null,"abstract":"<div><h3>Objective</h3><p>This study attempted to investigate the mechanism of miR-204-5p and its downstream gene in regulating bio-functions of esophageal cancer (EC).</p></div><div><h3>Methods</h3><p>Bioinformatics analysis was performed to select the mature miRNAs<span><span>, mRNAs, and clinical data of EC. The miRNA-mRNA regulatory axis was predicted through bioinformatics and used Dual-luciferase analysis to verify the interaction between miR-204-5p and APLN. qRT-PCR was applied to analyze expression of miR-204-5p and APLN mRNA. Western blot was utilized to detect APLN </span>protein expression. Functional assays like CCK-8, wound healing, Transwell, and stem cell sphere formation assays were launched to confirm proliferative, migratory, invasive and stemness of cells in different treatment groups.</span></p></div><div><h3>Results</h3><p>MiR-204-5p was lowly expressed while its target gene APLN was highly expressed in tumor tissues. Besides, miR-204-5p overexpression hindered proliferation, invasion, migration, and stemness of EC cells. Additionally, dual-luciferase assay verified the interaction of miR-204-5p and APLN. MiR-204-5p could downregulate APLN level and its overexpression reduced the effect of APLN on EC cell functions.</p></div><div><h3>Conclusion</h3><p>Dysregulation of miR-204-5p/APLN axis was linked with malignant progression of EC. MiR-204-5p/APLN may be an underlying candidate for the design of anticarcinogens.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111791"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10359508","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}
Lung adenocarcinoma (LUAD) is featured in high morbidity and mortality. Aberrant activation of the histone methyltransferase EZH2 has close association with cancer progression. This research aimed to deeply dive into the role and possible molecular mechanisms of EZH2 and its downstream genes in malignant progression and DNA damage repair of LUAD cells.
Methods
Expression of EZH2 in LUAD cells was analyzed by qRT-PCR, and the effects of EZH2 on proliferation, and apoptosis of LUAD cells were examined by CCK-8, colony formation and flow cytometry assays. The downstream targets of EZH2 were predicted by bioinformatics analysis. Then, the targeting relationship between EZH2 and RAI2 was examined by CHIP and luciferase reporter assays. Rescue assay were used to further validate the effect of EZH2/RAI2 on the malignant progression of LUAD cells. The expression levels of EZH2, RAI2 and p53 were examined by Western blot.
Results
Upregulation of EZH2 was identified in LUAD tissues and cells. RAI2 was a downstream target gene of EZH2, and the two were negatively correlated. Silencing EZH2 suppressed proliferation of LUAD cells, promoted expression of p53, cell cycle arrest and apoptosis. While silencing RAI2 could reverse the above-mentioned effects caused by EZH2 silencing.
Conclusion
These results demonstrated that EZH2 promoted malignant progression and DNA damage repair of LUAD cells by targeting and negatively regulating RAI2.
{"title":"EZH2 affects malignant progression and DNA damage repair of lung adenocarcinoma cells by regulating RAI2 expression","authors":"Mingjiang Huang, Jianyang Ding, Xuhui Wu, Xuyang Peng, Gongzhi Wu, Congxiong Peng, Huaizhong Zhang, Chaofan Mao, Bin Huang","doi":"10.1016/j.mrfmmm.2022.111792","DOIUrl":"10.1016/j.mrfmmm.2022.111792","url":null,"abstract":"<div><h3>Background</h3><p>Lung adenocarcinoma<span> (LUAD) is featured in high morbidity and mortality. Aberrant activation of the histone methyltransferase<span> EZH2 has close association with cancer progression. This research aimed to deeply dive into the role and possible molecular mechanisms of EZH2 and its downstream genes in malignant progression and DNA damage repair of LUAD cells.</span></span></p></div><div><h3>Methods</h3><p><span>Expression of EZH2 in LUAD cells was analyzed by qRT-PCR, and the effects of EZH2 on proliferation, and apoptosis of LUAD cells were examined by CCK-8, colony formation and flow cytometry assays. The downstream targets of EZH2 were predicted by bioinformatics analysis. Then, the targeting relationship between EZH2 and RAI2 was examined by CHIP and </span>luciferase<span> reporter assays. Rescue assay were used to further validate the effect of EZH2/RAI2 on the malignant progression of LUAD cells. The expression levels of EZH2, RAI2 and p53 were examined by Western blot.</span></p></div><div><h3>Results</h3><p>Upregulation of EZH2 was identified in LUAD tissues and cells. RAI2 was a downstream target gene of EZH2, and the two were negatively correlated. Silencing EZH2 suppressed proliferation of LUAD cells, promoted expression of p53, cell cycle arrest and apoptosis. While silencing RAI2 could reverse the above-mentioned effects caused by EZH2 silencing.</p></div><div><h3>Conclusion</h3><p>These results demonstrated that EZH2 promoted malignant progression and DNA damage repair of LUAD cells by targeting and negatively regulating RAI2.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111792"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10709509","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}
Pub Date : 2022-07-01DOI: 10.1016/j.mrfmmm.2022.111793
Zhuoya Dai, Hongqin Luo, Jingdong Chen, Liang Li
Background
Biological mechanism of miR-210-3p in endometrial carcinoma (EC) remains unclear. Here, our purpose is to study effects of miR-210-3p on malignant progression of EC.
Methods
Bioinformatics analysis showed miRNA and mRNA are abnormally expressed in EC tissues. Quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) was utilized to compare miR-210-3p mRNA level in EC cells and tissues. qRT-PCR and western blot were used to measure RUNX1T1 and NCAM1 at mRNA and protein levels, and western blot for p-AKT and AKT proteins related to PI3K/AKT signaling pathway. Furthermore, EC cell behaviors were assayed via Cell Counting Kit-8, cell colony formation assay, wound healing, transwell and flow cytometry experiments. Interaction between RUNX1T1 and miR-210-3p was verified through dual-luciferase assay. Immunohistochemistry was used to analyze RUNX1T1 expression in clinical samples
Results
MiR-210-3p was considerably upregulated and RUNX1T1 was significantly under-expressed in EC. Overexpression of miR-210-3p stimulated cell proliferation, migration, invasion, and restrained cell apoptosis in EC. Dual-luciferase assay proved that RUNX1T1 was a target gene of miR-210-3p. The level of RUNX1T1 in EC was downregulated after overexpressing miR-210-3p. Rescue assay showed that overexpression of RUNX1T1 had an inhibitory impact on tumor-relevant cell behaviors, whereas overexpression of miR-210-3p rescued such inhibition. Overexpression of RUNX1T1 reduced p-AKT expression, which was restored with concomitantly overexpressed miR-210-3p.
Conclusion
In general, miR-210-3p behaves as an oncogene in EC by down-regulating the expression of RUNX1T1. This study elucidates a new functional mechanism in EC, and indicates miR-210-3p an underlying target.
{"title":"MiR-210-3p accelerates tumor-relevant cell functions of endometrial carcinoma by repressing RUNX1T1","authors":"Zhuoya Dai, Hongqin Luo, Jingdong Chen, Liang Li","doi":"10.1016/j.mrfmmm.2022.111793","DOIUrl":"10.1016/j.mrfmmm.2022.111793","url":null,"abstract":"<div><h3>Background</h3><p>Biological mechanism of miR-210-3p in endometrial carcinoma (EC) remains unclear. Here, our purpose is to study effects of miR-210-3p on malignant progression of EC.</p></div><div><h3>Methods</h3><p><span>Bioinformatics analysis showed miRNA and mRNA are abnormally expressed in EC tissues. Quantitative real-time fluorescence </span>polymerase chain reaction<span><span><span> (qRT-PCR) was utilized to compare miR-210-3p mRNA level in EC cells and tissues. qRT-PCR and western blot were used to measure </span>RUNX1T1 and NCAM1 at mRNA and protein levels, and western blot for p-AKT and AKT proteins related to PI3K/AKT </span>signaling pathway. Furthermore, EC cell behaviors were assayed via Cell Counting Kit-8, cell colony formation assay, wound healing, transwell and flow cytometry experiments. Interaction between RUNX1T1 and miR-210-3p was verified through dual-luciferase assay. Immunohistochemistry was used to analyze RUNX1T1 expression in clinical samples</span></p></div><div><h3>Results</h3><p>MiR-210-3p was considerably upregulated and RUNX1T1 was significantly under-expressed in EC. Overexpression of miR-210-3p stimulated cell proliferation, migration, invasion, and restrained cell apoptosis in EC. Dual-luciferase assay proved that RUNX1T1 was a target gene of miR-210-3p. The level of RUNX1T1 in EC was downregulated after overexpressing miR-210-3p. Rescue assay showed that overexpression of RUNX1T1 had an inhibitory impact on tumor-relevant cell behaviors, whereas overexpression of miR-210-3p rescued such inhibition. Overexpression of RUNX1T1 reduced p-AKT expression, which was restored with concomitantly overexpressed miR-210-3p.</p></div><div><h3>Conclusion</h3><p>In general, miR-210-3p behaves as an oncogene in EC by down-regulating the expression of RUNX1T1. This study elucidates a new functional mechanism in EC, and indicates miR-210-3p an underlying target.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111793"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10358565","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}
Increasing evidence shows that Transmembrane 4 L6 family member 1(TM4SF1) exerts a critical role in mediating the progression of various tumors. Nevertheless, the exact mechanism of TM4SF1 in gastric cancer (GC) remains unclear.
Methods
Bioinformatics analysis was utilized to analyze TM4SF1 expression in GC tissues. Also, MiRWalk and starBase databases were used to predict the upstream microRNAs which could regulate TM4SF1 expression. Gene set enrichment analysis (GSEA) for TM4SF1 was conducted to screen the potentially involved pathways. Dysregulation of microRNA-501–3p/TM4SF1 was implemented to investigate the regulatory roles of these genes in GC. qRT-PCR and western blot were employed to measure the expression changes of microRNA-501–3p, TM4SF1, and epithelial-mesenchymal transition (EMT) signaling pathway-associated proteins. CCK-8, colony formation, and transwell assays were introduced to examine the biological functions of GC cell lines.
Results
TM4SF1 presented a significantly low level in mRNA and protein in GC cells. MicroRNA-501–3p could target TM4SF1 and reduce its expression. Cell function experiments revealed that microRNA-501–3p facilitated cell proliferation, migration, and invasion, while inhibiting cell apoptosis in GC by targeting TM4SF1. EMT-associated proteins were altered by changing microRNA-501–3p/TM4SF1 axis.
Conclusion
MicroRNA-501–3p regulated EMT signaling pathway by down-regulating TM4SF1 expression and therefore facilitated the malignant progression of GC, which may provide a new potential therapeutic target for the treatment of GC patients.
{"title":"MicroRNA-501-3p targeting TM4SF1 facilitates tumor-related behaviors of gastric cancer cells via EMT signaling pathway","authors":"Yunhai Wei, Lei Yin, Xiao Xie, Zhongxin Wu, Jinyu Zhang, Yuhai Gao, Jianing Tang","doi":"10.1016/j.mrfmmm.2022.111802","DOIUrl":"10.1016/j.mrfmmm.2022.111802","url":null,"abstract":"<div><h3>Background</h3><p>Increasing evidence shows that Transmembrane 4 L6 family member 1(TM4SF1) exerts a critical role in mediating the progression of various tumors. Nevertheless, the exact mechanism of TM4SF1 in gastric cancer (GC) remains unclear.</p></div><div><h3>Methods</h3><p>Bioinformatics analysis was utilized to analyze TM4SF1 expression in GC tissues. Also, MiRWalk and starBase databases were used to predict the upstream microRNAs<span><span> which could regulate TM4SF1 expression. Gene set enrichment analysis (GSEA) for TM4SF1 was conducted to screen the potentially involved pathways. Dysregulation of microRNA-501–3p/TM4SF1 was implemented to investigate the regulatory roles of these genes in GC. qRT-PCR and </span>western blot were employed to measure the expression changes of microRNA-501–3p, TM4SF1, and epithelial-mesenchymal transition (EMT) signaling pathway-associated proteins. CCK-8, colony formation, and transwell assays were introduced to examine the biological functions of GC cell lines.</span></p></div><div><h3>Results</h3><p>TM4SF1 presented a significantly low level in mRNA and protein in GC cells. MicroRNA-501–3p could target TM4SF1 and reduce its expression. Cell function experiments revealed that microRNA-501–3p facilitated cell proliferation, migration, and invasion, while inhibiting cell apoptosis in GC by targeting TM4SF1. EMT-associated proteins were altered by changing microRNA-501–3p/TM4SF1 axis.</p></div><div><h3>Conclusion</h3><p>MicroRNA-501–3p regulated EMT signaling pathway by down-regulating TM4SF1 expression and therefore facilitated the malignant progression of GC, which may provide a new potential therapeutic target for the treatment of GC patients.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111802"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10728901","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}
Pub Date : 2022-07-01DOI: 10.1016/j.mrfmmm.2022.111799
Mohammed A. Al-Hamamah, Moureq R. Alotaibi, Sheikh F. Ahmad, Ahmed Nadeem, Mohamed S.M. Attia, Mushtaq A. Ansari, Saleh A. Bakheet, Mohammed M. Alanazi, Sabry M. Attia
Rheumatoid arthritis (RA), which is driven by persistent activation of the immune system, primarily affects the joints. Several reports have estimated the risk of gonadal disruptions in arthritic patients, with potential attributable risk factors such as treatments with the disease-modifying antirheumatic drugs and the influence of the disease itself. The FDA approved rituximab, a therapy for non-Hodgkin's lymphoma, for management of RA in February 2006. However, the influence of repeated treatment with rituximab on gonadal function in RA has not been reported yet. Thus, the aim of the presents study is to evaluate whether repeated treatment with the clinically relevant dose of rituximab may change the gonadal disruptions in collagen-induced arthritis in male DBA/1 J mouse, a model of RA. Testicular disruptions, as determined by the sperm DNA strand breaks, spermatocyte chromosomal analysis and spermiogram examination have been conducted by the use of standard techniques. Additionally, we aimed to test whether the anti-rheumatic effect of rituximab also decreases the cellular oxidant-antioxidant imbalance in arthritic male DBA/1 J mice. Repeated treatment of naïve control DBA/1 J mice with rituximab did not exhibit any significant deleterious effects. Moreover, repeated administration of rituximab to the arthritic DBA/1 J mice suppressed disease severity and decreased testicular disruptions. Rituximab treatment also diminished gonadal oxidative stress, through decreasing reactive oxygen species generation and restoring the reduced glutathione level in arthritic DBA/1 J mice. In conclusion, rituximab is a safe therapeutic agent and can mitigate gonadal disruptions induced by arthritis, which insinuates the importance for arthritic patients especially at reproductive age.
{"title":"Treatment with the anti-CD20 monoclonal antibody rituximab mitigates gonadal disruptions in the collagen-induced arthritis in male DBA/1 J mouse model","authors":"Mohammed A. Al-Hamamah, Moureq R. Alotaibi, Sheikh F. Ahmad, Ahmed Nadeem, Mohamed S.M. Attia, Mushtaq A. Ansari, Saleh A. Bakheet, Mohammed M. Alanazi, Sabry M. Attia","doi":"10.1016/j.mrfmmm.2022.111799","DOIUrl":"10.1016/j.mrfmmm.2022.111799","url":null,"abstract":"<div><p><span><span>Rheumatoid arthritis<span><span> (RA), which is driven by persistent activation of the immune system, primarily affects the joints. Several reports have estimated the risk of gonadal disruptions in arthritic patients, with potential attributable risk factors such as treatments with the disease-modifying antirheumatic drugs and the influence of the disease itself. The FDA approved rituximab, a therapy for non-Hodgkin's lymphoma, for management of RA in February 2006. However, the influence of repeated treatment with rituximab on </span>gonadal function<span><span> in RA has not been reported yet. Thus, the aim of the presents study is to evaluate whether repeated treatment with the clinically relevant dose of rituximab may change the gonadal disruptions in collagen-induced arthritis in male DBA/1 J mouse, a model of RA. Testicular disruptions, as determined by the sperm DNA strand breaks, </span>spermatocyte chromosomal analysis and spermiogram examination have been conducted by the use of standard techniques. Additionally, we aimed to test whether the anti-rheumatic effect of rituximab also decreases the cellular oxidant-antioxidant imbalance in arthritic male DBA/1 J mice. Repeated treatment of naïve control DBA/1 J mice with rituximab did not exhibit any significant deleterious effects. Moreover, </span></span></span>repeated administration<span><span> of rituximab to the arthritic DBA/1 J mice suppressed disease severity and decreased testicular disruptions. Rituximab treatment also diminished gonadal oxidative stress, through decreasing </span>reactive oxygen species generation and restoring the </span></span>reduced glutathione level in arthritic DBA/1 J mice. In conclusion, rituximab is a safe therapeutic agent and can mitigate gonadal disruptions induced by arthritis, which insinuates the importance for arthritic patients especially at reproductive age.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111799"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10351756","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}
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