Molecular & Cellular Toxicology最新文献

{"title":"CircNFIX promotes stemness and evasion of phagocytosis in glioma stem cells by sponging miR-449a to upregulate the expression of CD47","authors":"Yuanwei Fu, Zhizhao Qu, Rui Bai, Liu Yang, Hongqin Wang","doi":"10.1007/s13273-024-00475-1","DOIUrl":"https://doi.org/10.1007/s13273-024-00475-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Cancer stem cells play important roles in tumorigenesis and progression of glioma. Circular RNA nuclear factor I X (circNFIX, hsa_circ_0049658) has been found to facilitate the development of glioma. The regulation of circNFIX in glioma stem cells (GSCs) has never been studied.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>RNA levels of circNFIX, microRNA-449a (miR-449a) and cluster of differentiation 47 (CD47) were detected through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein analysis was performed by western blot. Cell proliferation and self-renewal abilities were assessed by EdU assay and tumor sphere formation assay. The macrophage-mediated phagocytosis and cytotoxicity were examined by flow cytometry and lactate dehydrogenase (LDH) assay, respectively. The target analysis was performed using dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down assays. In vivo assay was conducted through GSCs model in mice.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The levels of circNFIX and CD47 were upregulated in glioma tissues and GSCs. Silencing circNFIX or CD47 suppressed proliferation and self-renewal abilities but enhanced phagocytosis and cytotoxicity in GSCs. CircNFIX induced the positive regulation of CD47 by exerting the sponge effect on miR-449a in GSCs. The regulatory role of circNFIX was achieved by targeting miR-449a in GSCs. CircNFIX downregulation also repressed tumorigenesis of glioma and maintenance of stem cells by the miR-449a/CD47 axis in GSCs model in vivo.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The evidence suggested that circNFIX acted as a miR-449a sponge to regulate the CD47 level, thereby promoting the features of glioma stem cells and the evasion of phagocytosis.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"49 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783241","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":"Mangiferin can alleviate atopic dermatitis-like responses in mice and HaCaT cells","authors":"Cuilin Xie, MengYao Hu, Bin Niu","doi":"10.1007/s13273-024-00476-0","DOIUrl":"https://doi.org/10.1007/s13273-024-00476-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Atopic dermatitis (AD) is a chronic inflammatory disorder that can affect the physical and psychological health of individuals worldwide. Mangiferin has been previously shown to alleviate allergic diseases.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To investigate the effect of mangiferin on AD-like pathologies and the mechanism of action.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>After establishing a mouse model of AD by challenging male BALB/c mice with 1% 2,4-dinitrochlorobenzene (DNCB), 10, 50, and 100 mg/kg mangiferin was administered orally for 21 days. Scratching behaviors, dermatitis score, spleen weight, and serum immunoglobulin E (IgE) levels were assessed. Histopathological changes were determined using toluidine blue and hematoxylin–eosin staining. A cellular model of AD was established by co-stimulating HaCaT keratinocytes with tumor necrosis factor (TNF)-α and interferon (IFN)-γ. The mRNA expression of chemokines and Th2-related cytokines was examined using RT-qPCR. Western blot and immunofluorescence were used to detect the protein levels of markers of the AKT/NF-κB/STAT1 and MAPK pathways.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Mangiferin exhibited anti-atopic effects in DNCB-induced AD-like mice as evidenced by decreased scratching behaviors, dermatitis score, spleen weight, IgE levels, skin thickness, and mast cell infiltration in mice. Additionally, mangiferin inhibited expression of chemokines and Th2 type cytokines (IL-4, IL-5, and IL-13) in AD-like mice and TNF-α/IFN-γ-co-stimulated HaCaT cells. Moreover, mangiferin attenuated TNF-α/IFN-γ-induced release of various inflammatory factors (such as TNF-α, IL-1β, and IL-6) in HaCaT cells. Mangiferin repressed the activation of the AKT/NF-κB/STAT1 and MAPK signaling pathways under both in vivo and in vitro conditions.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Overall, mangiferin inhibits the inflammatory and pruritic responses in AD, which might be an effective drug for AD treatment.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"47 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744839","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":"Stress granule reporter system to assess perfluorooctanoic acid gastric toxicity in vitro","authors":"Jung-Min Lee, Kee K. Kim, Eun-Mi Kim","doi":"10.1007/s13273-024-00474-2","DOIUrl":"https://doi.org/10.1007/s13273-024-00474-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Perfluorooctanoic acid (PFOA) and its alternative compound, hexafluoropropylene oxide dimer acid (HFPO-DA), are commonly used in cookware and food packaging because they are structurally stable and have a long half-life. This allows them to enter the human body, where they accumulate and have potentially harmful effects on human health. While the ability of PFOA to induce various cytotoxicities, including endoplasmic reticulum (ER) stress, has been studied extensively, little is known about the effects of alternative compounds, such as HFPO-DA, on cells.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>This study aimed to evaluate the gastrointestinal toxicity of PFOA and HFPO-DA in vitro using a gastrointestinal AGS cell line. We established a real-time stress granule reporter system in human gastrointestinal cell lines by inserting green fluorescent protein into the Ras-GTPase-activating protein SH3-domain-binding protein 1 gene using CRISPR/Cas9-mediated homologous recombination.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We found that PFOA induced the phosphorylation of PERK, which is activated by ER stress in AGS cells, and in contrast, the alternative compound HFPO-DA did not induce the phosphorylation of PKR-like endoplasmic reticulum kinase under the same conditions as PFOA.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Based on our results, we concluded that, unlike PFOA, HFPO-DA does not induce ER stress, suggesting that it is less toxic than PFOA. However, the risks of HFPO-DA cannot be dismissed completely, and further studies comprising different stress conditions are needed to accurately predict the potential risks of alternative compounds, such as HFPO-DA.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"10 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744840","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":"Desflurane restrains renal ischemia–reperfusion-stimulated endoplasmic reticulum stress and apoptosis via elevating microRNA-181c-5p to target DNA damage-inducible transcript 4","authors":"JunFu Liu, Hui Chen, Shiying Huang","doi":"10.1007/s13273-024-00471-5","DOIUrl":"https://doi.org/10.1007/s13273-024-00471-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Renal ischemia/reperfusion injury (RI/RI) is the crucial cause of acute kidney injury.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The study was to explore the action mechanism of desflurane (DFE) pretreatment on RI/RI in rats. The RI/RI model of rats was constructed, and serum renal function parameters (blood urea nitrogen and serum creatinine) were detected adopting corresponding commercial kits to assess renal function injury. Detection of renal tissue damage was performed. Test of cell apoptosis was implemented. Examination of endoplasmic reticulum stress (ERS)-associated proteins C/EBP homologous protein, glucose regulatory protein 78, and activation transcription factor 6 was performed. Test of concentrations of interleukin-1β and tumor necrosis factor-αwas implemented.</p><h3 data-test=\"abstract-sub-heading\">Result</h3><p>The results illustrated DFE restrained renal ischemia–reperfusion (RIR)-stimulated ERS and apoptosis, and DFE elevated miR-181c-5p and suppressed DDIT4 inRIR rats. MicroRNA (miR)-181c-5p was declined in RIR rats and ameliorated ischemia–reperfusion-stimulated ERS and apoptosis, suppressive miR-181c-5p or elevated DDIT4 turned around the protection of DFE on RIR. MiR-181c-5p targeted DNA damage-inducible transcript 4 (DDIT4).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The study offered theoretical foundation for further exploration on DFE in repressing RIR-stimulated ERS and apoptosis via elevating miR-181c-5p to target DDIT4.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"24 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141610123","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":"Zearalenone activates GnRH neurons related to central precocious puberty by regulating microRNA-384/GPER signaling","authors":"Yan Sun","doi":"10.1007/s13273-024-00470-6","DOIUrl":"https://doi.org/10.1007/s13273-024-00470-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Central precocious puberty (CPP) is an important issue, characterized as the same physical features as normally timed puberty occurs at an early age. Non-steroidal mycotoxins such as zearalenone (ZEA) are the important triggering factors for CPP development in girls; however, the detailed mechanism responsible for the effect of ZEA is still unclear.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>In this study, the effect as well as the underlying mechanism of ZEA on cell proliferation and GnRH secretion in the mouse GnRH (gonadotropin-releasing hormone)-producing hypothalamic cell line GT1-7 were investigated.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The in vitro experiments revealed that ZEA treatment up-regulated cell proliferation as well as the expressions of GnRH and GPER (G protein-coupled estrogen receptor) in GT1-7 cells by down-regulating the expression of microRNA-384 (miR-384). However, such effects were attenuated by GPER inhibitor G15 pre-treatment. In addition, clinical samples analysis revealed that urinary ZEA in CPP patients significantly correlated to blood expressions of GPER and miR-384.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In conclusion, this study reveals a novel mechanism of ZEA on CPP using in vitro model and clinical samples, and which may provide a potential therapeutic target as well as the diagnostic biomarker for CPP.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"38 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141524903","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":"Silencing circRUFY1 protects retinal ganglion cell injury in acute intraocular hypertension by activating the ERK pathway through miR-196a-5p/CALM3 axis","authors":"BinBin Li, ShaoJun Li, Wei Tang, Min Zeng","doi":"10.1007/s13273-024-00469-z","DOIUrl":"https://doi.org/10.1007/s13273-024-00469-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Neuroinflammation has been recognized as a key pathological event in acute glaucoma. Medical treatment of acute glaucoma has mainly focused on lowering intraocular pressure, yet the majority of patients still experience deterioration. Aberrant expression or activity of circular RNAs in the retina has been described in various ophthalmic diseases.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study surveyed the mechanism of circRUFY1 in acute ocular hypertension (AOH)-induced retinal ganglion cell (RGC) injury.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>AOH rats expressed high circRUFY1 and CALM3, and low miR-196a-5p in the retina tissue. CircRUFY1 silencing in AOH-induced rats reduced the severity of retinal damage and RGC damage. CircRUFY1, as a ceRNA of miR-196a-5p, upregulated CALM3, and CALM3 overexpression could further activate the ERK pathway signaling in RGCs.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Silence of circRUFY1 protects RGCs from AOH injury mainly by inhibiting the ERK signaling pathway by regulating the miR-196a-5p/CALM3 axis. Overall, targeted intervention of circRUFY1 expression is a promising therapeutic strategy for treating RGC damage in acute glaucoma.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"11 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500966","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 therapeutic potential of Laggera alata in alleviating inflammation and oxidative stress: insights into the miR-150-5p/TRIM8 axis","authors":"JiangCun Wei, Sen Liang, Peng Yang, Bing Qing, JiaBao Ma, LeiMin Jiang, QingMei Deng, Wen Zhong, MingGang Wang, ZuJie Qin","doi":"10.1007/s13273-024-00468-0","DOIUrl":"https://doi.org/10.1007/s13273-024-00468-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This research was conducted to study the protective effect of <i>Laggera alata</i> (TPLA) on sepsis-induced liver injury (SLI).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The SLI model was established in rats by cecal ligation and puncture (CLP), and human liver THLE-3 cells were induced by LPS to establish a cellular SLI model. HE staining and TUNEL staining were performed on the liver tissue of SLI rats treated with TPLA. The effects of TPLA on THLE-3 cells were studied using CCK-8, flow cytometry, ELISA, and biochemical analysis. The functional mechanism of TPLA, miR-150-5p, and TRIM8 in SLI was studied.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>TPLA treatment improved SLI in CLP rats and LPS-induced human liver THLE-3 cell injury was manifested by liver tissue injury recovery and decreased apoptosis of liver cells. At the same time, inflammation and oxidative stress were also alleviated. miR-150-5p level was reduced in SLI rats and cells, while TPLA pretreatment restored miR-150-5p level. miR-150-5p inhibitors could impair the therapeutic effect of TPLA in THLE-3 cell damage. TRIM8 was a direct target of miR-150-5p, and there was a negative regulatory relationship between the miR-150-5p and TRIM8 mRNA levels. Overexpressing TRIM8 also weakened the therapeutic effect of TPLA on THLE-3 cell damage.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>TPLA reduces TRIM8 expression by upregulating miR-150-5p, thereby reducing inflammatory response and oxidative stress, and thus significantly alleviating SLI.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"89 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500841","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":"Hesperidin protects C2C12 myoblasts from oxidative damage by reducing ROS-mediated mitochondrial damage and endoplasmic reticulum stress","authors":"Yung Hyun Choi","doi":"10.1007/s13273-024-00446-6","DOIUrl":"https://doi.org/10.1007/s13273-024-00446-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Hesperidin, a flavanone glycoside found primarily in the peel of citrus fruits, has benefits as a natural compound for preventing various diseases, but its inhibitory effect against oxidative injury in muscle cells has not been reported.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The current study aimed to investigate whether hesperidin can prevent oxidative damage in C2C12 murine myoblasts.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Hesperidin was able to inhibit cytotoxicity while blocking hydrogen peroxide (H₂O₂) H₂O₂-induced DNA damage and apoptosis. Hesperidin also significantly improved the antioxidant capacity of C2C12 cells exposed to H₂O₂ by suppressing cellular reactive oxygen species production and increasing glutathione level. Additionally, H₂O₂-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress were effectively attenuated in the presence of hesperidin. Moreover, hesperidin neutralized H₂O₂-induced calcium ion (Ca²⁺) overload in mitochondria and mitigated the expression of cytosolic Ca²⁺-dependent proteases.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>These results imply that hesperidin protects against mitochondrial impairment and Ca²⁺-mediated ER stress by minimizing oxidative stress, thereby suppressing H₂O₂-induced cytotoxicity in C2C12 myoblasts.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"32 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500840","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":"Nuclear translocation of β-catenin and migration of arecoline-induced oral cancer cells reduced by Taiwanin E via p-GSK3β downregulation","authors":"Chi-Cheng Li, Marthandam Asokan Shibu, Wei-Wen Kuo, Yueh-Hsiung Kuo, Yun-Peng Chao, Chun-Hsu Yao, Da-Tian Bau, Pei-Jei Lio, Chung-Jen Chiang, Chih-Yang Huang","doi":"10.1007/s13273-024-00464-4","DOIUrl":"https://doi.org/10.1007/s13273-024-00464-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Oral squamous cell carcinomas (OSCCs) accounts for 90% of the total oral cancers and is a major public health issue worldwide. It is the most prevalent malignant epithelial neoplasm of the oral cavity.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>In this study, we analyzed the effect of Taiwanin E, a bioactive compound derived from Taiwania (<i>Taiwania cryptomerioides</i> Hayata), on metastasis and migration and further checked the mechanism particularly by Wnt signaling which is one of the key cascades involved in cancer.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Taiwanin E considerably attenuated the cell migratory potential of oral cancer cells in a dose-dependent manner. At the molecular level, it was found that Taiwanin E interfered with nuclear translocation of β-catenin via p-GSK3β specifically in tumor derived cells (T28) and not in non-tumor (N28) cells. Moreover, Taiwanin E significantly downregulated the downstream metastatic protein c-myc and TBX3.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The present study demonstrates that Taiwanin E inhibits the elevated expression levels from the baseline β-catenin levels and thereby potentially inhibits the migratory effects of T28 cells.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"57 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500967","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_circ_0002454 controls cervical cancer cell growth and metastasis by targeting SDC4 through miR-654-3p","authors":"Yanmei Li, Yuzhen Zhang, Fuqiang Xu, Nan Wang, Qing Liu","doi":"10.1007/s13273-024-00467-1","DOIUrl":"https://doi.org/10.1007/s13273-024-00467-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Circular RNAs (circRNAs) are involved in tumor growth and metastasis. The aim of this study was to elucidate the possible role of has_circ_0002454 in cervical cancer (CC) and its potential molecular mechanism.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>has_circ_0002454, miR-654-3p, and SDC4 mRNA levels were determined by RT-qPCR, and SDC4 protein was by Western Blot. Cell proliferation was detected by MTT, colony formation, and wound healing. Invasion and migration capacities of cells were assessed by Transwell assays. The targeting relationship between miR-654-3p and has_circ_0002454 or SDC4 was confirmed by dual-luciferase reporter gene and RIP assay. Xenograft tumor model was constructed to determine the role of has_circ_0002454 in CC.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In CC tissues and cell lines, has_circ_0002454 was associated with significantly higher SDC4 levels and significantly lower miR-654-3p expression. Down-regulation of has_circ_0002454 promoted miR-654-3p expression while decreasing SDC4 expression levels. has_circ_0002454 competitively bound miR-654-3p, and elevated miR-654-3p expression rescued the effects of has_circ_0002454 silencing on cancer cell proliferation, apoptosis, migration, and invasion. miR-654-3p directly targeted SDC4, and overexpression of SDC4 reversed the effect of has_circ_0002454 knockdown on cancer cell function. In addition, down-regulation of has_circ_0002454 effectively suppressed tumor growth in vivo.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>has_circ_0002454 reduction weakens the cancer phenotype of CC cells by modulating the miR-654-3p/SDC4 axis.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"63 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500842","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}