Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer最新文献

{"title":"NLRP3-Inflammasome Gene Variations in the Risk of Type 2 Diabetes.","authors":"C. Ozbayer, H. Kurt, Emine Yagci, M. Kebapçı, H. Gunes, I. Degirmenci","doi":"10.1615/jenvironpatholtoxicoloncol.2021040001","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021040001","url":null,"abstract":"Inflammation is the natural immunological response of an organism against any harmful, foreign or destructive effect to heal and repair damaged tissue. The nod-like receptor pyrin domain-containing-3 (NLRP3) inflammasome is one of the main components of the inflammatory mechanism and is associated with many inflammatory diseases, but it is also closely related to metabolic abnormalities, such as type 2 diabetes mellitus (T2DM), insulin resistance and obesity. NLRP3 activates inflammation and causes interleukin-1β release, exogenous and endogenous danger signals, as well as insulin resistance. In this direction, we focus on the gene structure of NLRP3 in diabetes and accordingly, we aim to determine the relationship between eight gene variations in the NLRP3 gene and T2DM. We investigated the rs10802501, rs10733113, rs10754558, rs10925026, rs10925027, rs35829419, rs4612666 and rs4925659 single-nucleotide polymorphisms of NLRP3 gene using the Sequenom MassARRAY system in 100 T2DM patients and 100 control individuals. There were no significant differences between T2DM risk and the genotype frequencies of rs10802501, rs10733113, rs35829419 and rs10925026 variants (p > 0.05). However, significant genotype frequencies were determined for rs10925027 (p = 0.0013) and rs4925659 (p < 0.001). For the risk allele G of the rs10754558 variant, significant differences were found in the heterozygous and dominant model (p = 0.036, p = 0.033). The genotype distribution of the rs4612666 variant was significant only in the heterozygous model (p = 0.047). In this hospital-based case-control study, rs10925027, rs4925659 and rs10754558 variants were found to be closely related to T2DM risk. The rs10925027 CC genotype, rs4925659 GG genotype, rs10754558 GG and GC+GG genotypes of the NLRP3 were determined as important risk factors for the T2DM.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82465984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Features of Coronavirus and the COVID-19 Pandemic's Impact in India.","authors":"Ankur Jaiswal, V. Babu, M. Sethi, Basant Baishya, Pallavi Jaiswal, R. Joshi, Sudhir Jugran, B. Ramola, Avnish Kumar","doi":"10.1615/jenvironpatholtoxicoloncol.2022035706","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2022035706","url":null,"abstract":"The rapid transmission of COVID-19 infection around the world in a brief timeframe has caused an exponential decline in street traffic and other industrial activities in various parts of the world. The confined human collaboration with the nature at the time of this emergency has shown up as an advantage for Mother Nature after COVID-19 flare because the air present in the atmosphere and water flowing in river streams is upgrading and untamed life is blossoming. India, being consistently seen as the center of contamination due to a tremendous population, overwhelming road traffic and industries which contribute to heavy pollution prompting rise in air quality index for almost all the big cities of the country. However, after the announcement of lockdown because of COVID-19, the air quality begun to upgrade and other environmental variables, for example, water quality in streams and waterways have begun offering a positive hint towards restoration. This review gives a brief knowledge on the structure and genomic organization of novel coronavirus as well as it focuses on alterations in air and water quality along with its environmental consequences at specific locations of the country during lockdown due to this pandemic circumstance.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83033154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abies spectabilis-Mediated Silver Nanoparticles Inhibits Cell Growth and Promotes Apoptosis in Breast Cancer MCF-7 Cells.","authors":"Guanghui Ren, Xiaoyan Hao, Shuyi Yan, Jun Chen, Guobin Qiu, K. Ang, Mohd Islahuddin Mohd Tamrin","doi":"10.1615/jenvironpatholtoxicoloncol.2021039805","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039805","url":null,"abstract":"Breast cancer is the second most cause of mortality among women worldwide due to the uncontrolled proliferation of tumor cells in the mammary epithelial tissues. The silver nanoparticles were formulated from the Abies spectabilis leaf (AS-AgNPs) and characterized by various practices like UV-vis spectroscopy, FTIR, SEM, and XRD. The in vitro anticancer potential of fabricated AS-AgNPs against the MCF-7 cells were analyzed. The MTT test was executed to investigate the cytotoxic nature of fabricated AS-AgNPs against MCF-7 cells. The magnitudes of ROS accumulation and MMP level in the AS-AgNPs supplemented MCF-7 cells were studied using fluorescent staining techniques. Caspase activities were studied using assay kits. The contents of oxidative stress and antioxidant biomarker (TBARS, SOD, CAT, and GSH) levels were scrutinized by standard methods. The expressions of apoptotic markers like Bax and Bcl-2 in the AS-AgNPs administered MCF-7 cells were detected by RT-PCR assay. The MTT findings showed that both extract and fabricated AS-AgNPs remarkably decreased the MCF-7 cells. Nonetheless, both plant extract and AS-AgNPs did not affect the cell viability of MCF-10A cells. Furthermore, the fabricated AS-AgNPs improved the ROS accumulation, and depleted the MMP status in the MCF-7 cells. AS-AgNPs administered MCF-7 cells demonstrated the improved TBARS content and depleted antioxidants. The treatment with AS-AgNPs considerably elevated the caspase-9 and -3 activities and Bax expression, while decreasing the Bcl-2 expression in MCF-7 cells. Hence the current investigation reports that the formulated AS-AgNPs exhibited remarkable in vitro anticancer action against MCF-7 cells through increased ROS, oxidative stress, and apoptotic protein expression. The fabricated AS-AgNPs could be a possible anticancer remedy in the future.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75430072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Targets of Nimbolide for Anti-Cancer Therapy: An Updated Review.","authors":"P. Elumalai, D. Ezhilarasan, S. Raghunandhakumar","doi":"10.1615/jenvironpatholtoxicoloncol.2021040263","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021040263","url":null,"abstract":"Cancer is a major cause of death worldwide with an increasing incidence rate and is considered a major public health problem. Distance metastasis to other tissues, high toxicity, and drug resistance of cancer cells to chemotherapy demand novel therapeutic approaches to treat cancer. Natural compounds from medicinal plants have been studied for therapeutic use in various malignancies. Nimbolide is an active principal compound from Azadirachta indica, which is an Asian traditional medicinal plant utilized historically as a remedy for a variety of diseases due to its antioxidant, anti-inflammatory, anti-cancer, and antimicrobial properties. It is a limonoid triterpene possessing potent anti-cancer effects in various types of cancers. It has been reported to induce multiple cytotoxic effects in tumor cells by modulating the cell proliferation, cell cycle, apoptosis, and metastasis by altering the various molecular signaling pathways. In the present review, we summarized all the in vitro and in vivo studies reporting the molecular targets of nimbolide for the therapeutic approaches in different types of cancer cells. We analyzed research publications up to September 2021 on the effect of nimbolide in various malignancies and the molecular mechanism of action. Nimbolide targets different signaling pathways including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), insulin like growth factor (IGF), Wingless and INT-1 (Wnt)/β-catenin, mitogen-activated protein kinases (MAPK)/c-Jun N-terminal kinases (JNK), phosphoinositide 3-kinase (PI3K)/AKT, tumor necrosis factor-α (TNF-α)/nuclear factor kappa B (NF-κβ), and death receptor 5 (DR5) in several cancer cells. Nimbolide's widespread availability and absence of side effects, as well as understanding the molecular mechanism of nimbolide's action, will be useful to develop a therapeutic agent against cancer.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83398543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rk2 Protects against Ulcerative Colitis via Inactivating ERK/MEK Pathway by SIRT1.","authors":"Xiaodong Huang, Jianwei Xiao, Mudan Wen, Jing-Tao Liang","doi":"10.1615/jenvironpatholtoxicoloncol.2021039648","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039648","url":null,"abstract":"BACKGROUND Chinese traditional medicine is widely used in the treatment of ulcerative colitis (UC). Ginsenoside Rk2 is a newly discovered dammarane triterpenoid saponin isolated from ginseng. Our study aimed to investigate the effects of Ginsenoside Rk2 on UC. METHODS Human clones of colorectal adenocarcinoma Caco-2 cells and human intestinal epithelial THP-1 cells were co-cultured to establish a UC model in vitro. Cell viability and apoptosis were analyzed by cell counting kit 8 (CCK-8) and flow cytometry assay, respectively. Inflammatory cytokines' mRNA levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Western blot was applied to examine the protein expression of apoptosis-associated proteins and the activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MEK) pathway. Furthermore, fisetin, an ERK kinase activator, was used to carry out rescue experiment. SRT1720, an activator of SIRT1, was applied to increase the SIRT1 protein levels while SIRT1 inhibitor nicotinamide (NAM) exerted the opposite effect. RESULTS Ginsenoside Rk2 promoted cell viability, suppressed cell apoptosis, and reduced the release of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α) of HT-29 cells in UC model in a concentration-dependent manner. Meanwhile, the inhibitory effects of Ginsenoside Rk2 on the ERK/MEK pathway strengthened with the increase of concentration, and was verified by fisetin application. Furthermore, the upregulation of SIRT1 induced by Ginsenoside Rk2 prompted dephosphorylation of ERK and MEK to attenuate ERK/MEK pathway activation and reduced inflammatory progress, which was confirmed by SRT1720 as well as NAM. CONCLUSIONS Ginsenoside Rk2 inactivated ERK/MEK pathway by regulating SIRT1 to restore the cellular function of human intestinal epithelial THP-1 cells. Therefore, Ginsenoside Rk2 may be effective in the treatment of UC.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84974243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and Characterization of Cadherin 6 (CDH6)-Targeting Chimeric Antigen Receptor (CAR) Modified T Cells.","authors":"Li Pang, Fang Ren, Xiaoxuan Xu, Lingyang Fu, Tifang Wang, Zhiqiang Guo","doi":"10.1615/jenvironpatholtoxicoloncol.2021040339","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021040339","url":null,"abstract":"In this study, we constructed cadherin 6 (CDH6)-targeting chimeric antigen receptor (CAR) modified T cells (CAR-T cells) and investigated their target-specific recognition and tumor-specific cytocidal effect through in vitro approach. CDH6 expression at the transcriptional level and its correlation with clinicopathological parameters in various tumor types were analyzed using online bioinformatics tool. Conventional molecular cloning method was used to construct the lentiviral vector encoding CDH6-specific CAR and the lentivirus was prepared using 3-plasmid transient cotransfection method. CDH6-targeting CAR-T cells were prepared using centrifugal infection method, and the specific recognition and cytocidal effects of CAR-T cell targets were investigated through in vitro co-culture experiments. At the transcription level, CDH6 was significantly overexpressed in ovarian cancer tissues (P < 0.05). Although it was not correlated with tumor stage and patient's prognosis, the overexpression of CDH6 was positively associated with the expression of paired-box 8 (PAX8), a lineage-specific transcription factor. In the present study, we successfully established CDH6-targeting CAR-T cells that can secrete effector cytokines and produce specific cytocidal effects after being co-cultured with CDH6-positive ovarian cancer cells in vitro. Thus, CDH6, as a lineage-specific factor of ovarian tissue, may be an ideal target for CAR-T cell therapy of ovarian cancer.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83097212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Effect of Arbutin on Diethylnitrosamine-Induced Liver Carcinoma in Rats via the GRP and GADD Pathway.","authors":"Xiangting Zeng, Haipeng Liu, Zeping Huang, Peng Dong, Xiao Chen","doi":"10.1615/jenvironpatholtoxicoloncol.2021039772","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039772","url":null,"abstract":"Liver cancer is the third most common cancer, with increasing morbidity and mortality rates worldwide. Despite the increasing occurrence of liver cancer, it has a poor prognosis and potential treatment options are still lacking. The current study aimed to explore the anticancer potential of arbutin against diethylnitrosamine (DEN)-triggered liver carcinogenesis in rats. Liver cancer was initiated in rats via the administration of DEN (200 mg/kg) and then treated with 30 mg/kg of arbutin. Albumin, globulin, and total protein were quantified using kits. Antioxidant, liver injury marker, and tumor biomarker contents were quantified using marker-specific assay kits. The inflammatory markers c-JNK, TRAIL, caspase-8, and p53 contents were also detected using kits. Reverse transcription PCR analysis was used to study the expression of chaperones GRP78, GRP94, and PDIA4 as well as ERDJ4, ATF4, and GADD34. Liver histology was studied microscopically. The arbutin treatment effectively improved body weight and reduced liver weight in animals with DEN-provoked liver cancer. The treatment also improved the albumin, globulin, and total protein contents and antioxidants. In addition, arbutin reduced liver injury marker enzyme function and improved c-JNK, TRAIL, caspase-8, and p53 contents. Arbutin supplementation also decreased the expression of GRP78, PDIA4, GRP94, ERDJ4, ATF4, and GADD34 in the liver tissues of DEN-provoked animals. Arbutin effectively ameliorated the DEN-provoked histological alterations. Altogether, our findings show that arbutin has anti-inflammatory, antioxidant, and anticarcinogenic activities against DEN-provoked liver cancer in rats.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90603323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sonochemical Internalization of Bleomycin Inhibits Adenocarcinoma Breast Tumor Development in an Orthotopic Rat Model.","authors":"Lina Nguyen, Ethan-Quan Nguyen, Cassandra Tran, K. Nguyen, Ananya Devarajan, K. Berg, H. Hirschberg","doi":"10.1615/jenvironpatholtoxicoloncol.2021040536","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021040536","url":null,"abstract":"One approach to reducing post-operative tumor recurrence and alleviate debilitating side effects of systemic chemotherapy, is work centered on the development of drug activation by focused and targeted externally applied physical energy thus providing site and temporal specificity. One such technique, light mediated photochemical internalization (PCI), has been shown to be a method to obtain enhanced chemotherapy efficacy for a wide variety of anti-cancer agents. A related technology, sonochemical internaization (SCI), is an extension of the PCI concept developed to overcome the limitations of poor light penetration in tissue. SCI utilizes ultrasonic energy, to activate sonosensitizers, co-administered with anti cancer agents. The purpose of the study reported here was to evaluate the inhibitory effects of SCI of bleomycin (BLM), both in vitro and in vivo, on the adenocarcinoma breast tumor rat cell line Mat B III. In vitro, the two aspects of sonication, sonoporation (SP) and sonochemical internalization (SCI) of BLM were examined. In vivo, BLM-SCI significantly inhibited tumor development, following Mat B III implantation, in an orthotopic breast tumor animal model using Fisher rats.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75296721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Allocryptopine on the Proliferation and Epithelial-Mesenchymal Transition of Oral Squamous Cell Carcinoma through m6A Mediated Hedgehog Signaling Pathway.","authors":"Junxia Gong, Chunlin Wang, Fang Zhang, Weidong Lan","doi":"10.1615/jenvironpatholtoxicoloncol.2021039718","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039718","url":null,"abstract":"BACKGROUND Allocryptopine is an isoquinoline alkaloid extracted from Macleaya cordata. This study aimed to explore the effects of allocryptopine on the growth and metastasis of oral squamous cell carcinoma (OSCC) cells. METHODS The human OSCC cell line HSC-3 and SAS were selected in this study. MTT assay was performed to measure cell viability. Western blot was used to detect protein expressions. transwell assay was conducted to determine the migrated and invaded cells. M6A modification was confirmed by methylated RNA immunoprecipitation assay. RESULTS Compared with the NC group, the cell viability, migration and invasion ability of OSCC cells were suppressed after allocryptopine treatment in a dose dependent manner. Allocryptopine upregulated the E-cadherin expression and downregulated N-cadherin and Vimentin expressions in the OSCC cells. In addition, the protein expressions of patched receptor 1 (PTCH1), smoothened co-receptor (SMO) and Gli family (GLI1) were downregulated after allocryptopine treatment. Furthermore, allocryptopine treatment decreased the expression of Methyltransferase like 3 (METTL3) and inhibited N6-methyladenosine (m6A) modification of PTCH1. Moreover, overexpression of PTCH1 reversed the effects of allocryptopine and induced the aggressiveness of OSCC cells. CONCLUSION Allocryptopine suppressed the proliferation and epithelial-mesenchymal transition (EMT) of OSCC cells via m6A mediated Hedgehog signaling pathway, relieving the carcinogenic behaviors of OSCC.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78315361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT1 Mediates the Transcription of CircIFI30 and Promotes the Progression of Triple-Negative Breast Cancer by Up-Regulating CDCA4.","authors":"Jie Zhang, Shufeng Xia, Xiao-you Liu, Deguang Qi, Xiao-song He, Daqin Chen","doi":"10.1615/jenvironpatholtoxicoloncol.2021039794","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039794","url":null,"abstract":"Signal transducers and activators of transcription 1 (STAT1) is an important transcription factor that regulates the growth, survival, differentiation and apoptosis of various tumor cells. However, the biological roles of STAT1 and potential mechanisms in triple-negative breast cancer (TNBC) remain largely unknown. The expression levels of STAT1, CircIFI30, CDCA4, and epithelial-mesenchymal transition (EMT)-associated molecules (MM2, MMP9, E-cadherin, and N-cadherin) were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Furthermore, cell-counting kit-8 assay, Transwell assay, flow cytometry, and immunofluorescence staining were performed to investigate the biological functions of STAT1 and CircIFI30 in TNBC cells. In addition, Dual luciferase activity assay and chromatin immunoprecipitation qPCR were used to predict the interaction between STAT1 and CircIFI30 promoter. The effects of CircIFI30 on the stability of CDCA4 mRNA were also confirmed in further function study. Up-regulation of STAT1 was detected in TNBC tissues and cells, which were positively correlated with tumor metastasis, advanced clinical stage and poor survival rate. Up-regulated STAT1 could promote the proliferation, invasion, migration, EMT and inhibit the apoptosis of TNBC cells. RNA-seq indicated has_circ_0005571 (CircIFI30) was significantly down-regulated in TNBC cells after knockdown of STAT1. Moreover, STAT1 could be novel transcription factor that binds to CircIFI30 promoter to enhance its transcription. Additionally, knockdown of CirclFl30 down regulated the expression of cell division cycleassociated protein 4 (CDCA4) through reducing the stability of its mRNA. Our data revealed the STAT1/CircIFI30/CDCA4 axis could regulate the proliferation, invasion, migration, EMT and apoptosis of TNBC cells. Therefore, STAT1 may be a putative therapeutic candidate for targeted treatment of TNBC.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83782094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}