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

{"title":"ALDH2 mutations and defense against genotoxic aldehydes in cancer and inherited bone marrow failure syndromes","authors":"Anthony Yiu-Ho Woo,&nbsp;Lina Jia","doi":"10.1016/j.mrfmmm.2024.111870","DOIUrl":"10.1016/j.mrfmmm.2024.111870","url":null,"abstract":"<div><p>Reactive aldehydes, for instance, formaldehyde and acetaldehyde, are important endogenous or environmental mutagens by virtue of their abilities to produce a DNA lesion called interstrand crosslink (ICL). Aldehyde-metabolizing enzymes such as aldehyde dehydrogenases (ALDHs) and the Fanconi anemia (FA) pathway constitute the main defense lines against aldehyde-induced genotoxicity. Biallelic mutations of genes in any one of the FA complementation groups can impair the ICL repair mechanism and cause FA, a heterogeneous disorder manifested by bone marrow failure (BMF), congenital abnormality and a strong predisposition to cancer. The defective <em>ALDH2</em> polymorphism rs671 (<em>ALDH2*2</em>) is a known risk and prognostic factor for alcohol drinking-associated cancers. Recent studies suggest that it also promotes BMF and cancer development in FA, and its combination with alcohol dehydrogenase 5 (ADH5) mutations causes aldehyde degradation deficiency syndrome (ADDS), also known by its symptoms as aplastic anemia, mental retardation, and dwarfism syndrome. <em>ALDH2*2</em> and another pathogenic variant in the alcohol-metabolizing pathway, <em>ADH1B1*1</em>, is prevalent among East Asians. Also, other <em>ALDH2</em> genotypes with disease-modifying potentials have lately been identified in different populations. Therefore, it would be appropriate to summarize current knowledge of genotoxic aldehydes and defense mechanisms against them to shed new light on the pathogenic effects of <em>ALDH2</em> variants together with other genetic and environmental modifiers on cancer and inherited BMF syndromes. Lastly, we also presented potential treatment strategies for FA, ADDS and cancer based on the manipulation of aldehyde-induced genotoxicity.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111870"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474098","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":"AQP5 promotes epithelial-mesenchymal transition and tumor growth through activating the Wnt/β-catenin pathway in triple-negative breast cancer","authors":"Zhengcai Zhu,&nbsp;Tao Li,&nbsp;Honggang Wang,&nbsp;Lianghe Jiao","doi":"10.1016/j.mrfmmm.2024.111868","DOIUrl":"10.1016/j.mrfmmm.2024.111868","url":null,"abstract":"<div><h3>Background</h3><p>Emerging data identifies aquaporin 5 (AQP5) as a vital player in many kinds of cancers. Over expression of AQP5 was associated with increased metastasis and poor prognosis, suggesting that AQP5 may facilitate cancer cell proliferation and migration. Our previous studies also showed that AQP3 and AQP5 were highly expressed in triple-negative breast cancer (TNBC) and the expression of AQP3 and AQP5 in TNBC tissue was positive correlated with advanced clinical stage.</p></div><div><h3>Objective</h3><p>We aim to investigate the role of AQP5 in TNBC oncogenesis and development.</p></div><div><h3>Methods</h3><p>MDA-MB-231 cells were transfected with siRNA-AQP5 and AQP5 overexpression vector to establish a differential expression system for AQP5. Cell proliferation and apoptosis of MDA-MB-231 cells were detected by CCK-8 (Cell Counting Kit-8) and FCM (flow cytometry), respectively. Cell migration and invasion abilities were evaluated by wound healing assay and transwell assay. The qRT-PCR and western blot assays were used to study the effect of AQP5 expression level on the expression of epithelial-to-mesenchymal transition (EMT) related molecules. The effects of ICG-001, a Wnt/β-catenin signaling pathway inhibitor, on the invasive and migratory capabilities of overexpressed AQP5 cells and downstream molecules were measured.</p></div><div><h3>Results</h3><p>1. The expression of AQP5 in the MDA-MB-231 cells was significantly higher than that in the MCF-10A cells. 2. Up-regulation of AQP5 significantly promoted the proliferation, migration and invasion of TNBC cells, while inhibited the cell apoptosis; in addition, up-regulation of AQP5 increased the expression of Bcl-2 and decreased the expression of Caspase-3. However, knockdown of AQP5 presented the adverse effects of AQP5 overexpression. 3. Overexpressed AQP5 induced the overexpression of EMT-related factors, which further promoted the migration and invasion of cells. 4. Overexpression of AQP5 could up-regulate the expression of β-catenin in the nucleus followed by increasing the expression levels of downstream genes in Wnt/β-catenin signaling pathway. Moreover, ICG-001, the inhibitor of Wnt/β-catenin signaling pathway, could significantly attenuate the effect of overexpression of AQP5 on cells, further confirming that AQP5 may promote the proliferation, migration and invasion of TNBC cells by activating Wnt/β-catenin signaling pathway.</p></div><div><h3>Conclusions</h3><p>In the TNBC cells, AQP5 modulates the expression levels of EMT-related proteins through activation of Wnt/β-catenin signaling pathway, thus enhancing the cell proliferation, migration and invasion while inhibiting the cell apoptosis.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111868"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500041","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":"HOXA1 promotes epithelial-mesenchymal transition and malignant characteristics of laryngeal squamous cell carcinoma","authors":"Jun Wu,&nbsp;Xiaofeng Gu","doi":"10.1016/j.mrfmmm.2024.111882","DOIUrl":"10.1016/j.mrfmmm.2024.111882","url":null,"abstract":"<div><p>Despite considerable advancements in the diagnosis and treatment of LSCC, there has been no significant improvement in survival rate. Consequently, identifying molecular targets for this cancer is of paramount importance. HOXA1, a constituent of the homeobox transcription factor cluster, plays a role in the development of various types of cancer. Nevertheless, the specific function and mechanism of HOXA1 in LSCC remains unclear. This study aimed to clarify the impact of HOXA1 on the advancement of LSCC and uncover its underlying mechanism. Our findings indicate that HOXA1 exhibits a significantly elevated expression level in LSCC. Suppression of HOXA1 inhibited the proliferation of LSCC cells. Furthermore, the ablation of HOXA1 triggered the apoptosis of LSCC cells and inhibited EMT. Functionally, HOXA1 has a role in initiating the activation of the PI3K/AKT/mTOR pathway in LSCC cells. In summary, HOXA1 significantly contributes to the EMT of LSCC cells via the PI3K/AKT/mTOR signaling pathway, thereby facilitating the proliferation and motility of LSCC cells. Consequently, HOXA1 presents itself as a viable therapeutic target for LSCC interventions.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111882"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147240","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 RAD51 S181P mutation shortens lifespan of female mice","authors":"Sherry G. Dodds ,&nbsp;Gene Hubbard ,&nbsp;Yong Jun Choi ,&nbsp;Kyungjae Myung ,&nbsp;Gene Elliot ,&nbsp;Lisa Garrett ,&nbsp;Tae Moon Kim ,&nbsp;Paul Hasty","doi":"10.1016/j.mrfmmm.2024.111878","DOIUrl":"10.1016/j.mrfmmm.2024.111878","url":null,"abstract":"<div><p>RAD51 is critical to the homologous recombination (HR) pathway that repairs DNA double strand breaks (DSBs) and protects replication forks (RFs). Previously, we showed that the S181P (SP) mutation in <em>RAD51</em> causes defective RF maintenance but is proficient for DSB repair. Here we report that SP/SP female mice exhibit a shortened lifespan compared to +/+ females but not males. Histological analysis found that most mice in this study died from lymphoma, independent of genotype and sex. We propose that a potential cause for shortened lifespan in SP/SP females is due to the RF defect.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111878"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0027510724000289/pdfft?md5=39f47dbaabdae7ba92ee31eea49d1079&pid=1-s2.0-S0027510724000289-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PM2.5 induces lung inflammation through ANGPTL4","authors":"Yeak-Wun Quek ,&nbsp;Yu-Ting Kang ,&nbsp;Hsu Chih Huang ,&nbsp;Hui-Yi Chang ,&nbsp;I-Chieh Huang ,&nbsp;Ko-Huang Lue ,&nbsp;Jiunn-Liang Ko","doi":"10.1016/j.mrfmmm.2024.111887","DOIUrl":"10.1016/j.mrfmmm.2024.111887","url":null,"abstract":"<div><div>Fine particulate matter (PM_2.5) is a common major air pollutant associated with decreased lung function, induced allergic airway inflammation closely correlated with chronic lung diseases. Angiopoietin-like protein 4 (ANGPTL4) is a cytokine with multiple functions, participating in processes such as inflammation, angiogenesis, and metastasis. Curcumin is an active compound found in turmeric plants and possesses various pharmacological effects, including antioxidant, anti-inflammatory, anticancer, and immunomodulatory properties. The aim of this study was twofold: firstly, to investigate the involvement of ANGPTL4 in lung inflammation and carcinogenesis under PM_2.5 exposure, and secondly, to explore the impact of curcumin on ANGPTL4 expression and its potential in lung cancer chemoprevention. We used protein array to detect several proinflammatory cytokines and then used qPCR to confirm by increasing the concentration of PM_2.5 to enhance the expressions of CXCL1, CXCL5; IL-1α, IL-1β, MIP-3α and inflammation- or fibrosis-associated proteins. Curcumin inhibits PM_2.5_-induced ANGPTL4 and the IκB-α (inhibitor of NFκB)-dependent inflammatory pathway. Silencing ANGPTL4 by shRNA restore IκB-α and MIP-3α expression. In conclusion, the increased expression of ANGPTL4 after treatment with PM_2.5 in lung cells may be one of the mechanisms by which PM_2.5 exposure contributes to lung inflammation progression. Our results provide evidence that curcumin in anti-inflammation therapeutics could serve as a beneficial chemopreventive agent.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111887"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634778","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":"miR-129–2-3p binds SEMA4C to regulate HCC development and inhibit the EMT","authors":"Siyuan Ma ,&nbsp;Chun Pu","doi":"10.1016/j.mrfmmm.2024.111872","DOIUrl":"10.1016/j.mrfmmm.2024.111872","url":null,"abstract":"<div><h3>Background</h3><p>Among primary liver cancers, HCC is the most prevalent. Small noncoding RNAs called miRNAs control the expression of downstream target genes to take part in a variety of physiological and pathological processes, including those related to cancer.</p></div><div><h3>Methods</h3><p>miR-129–2–3p and SEMA4C expression levels were assessed using RT-qPCR. The CCK-8, invasion, and wound healing assays were used to confirm the capacity of HCC cells for proliferation, invasion and migration respectively. Serum SEMA4C levels were detected via ELISA. The RIP and dual-luciferase reporter assays were used to confirm the existence of intergenic binding sites. Cell apoptosis assay and cell cycle assay were performed to detect the apoptosis rate and cycle distribution of cells, and WB was performed to detect the protein expression of SEMA4C, RhoA, ROCK1, E-cadherin, N-cadherin, and vimentin. Furthermore, cancer-inhibiting role of miR-129–2–3p were further confirmed by animal tests.</p></div><div><h3>Results</h3><p>miR-129–2–3p expression was reduced in HCC tissues and cells. Overexpression of miR-129–2–3p decreased the proliferation, invasion, migration, and EMT in HCC cells, whereas inhibition of miR-129–2–3p had the opposite effects. Our research also showed that SEMA4C was increased in HCC tissues, serum and cells, and that SEMA4C knockdown prevented HCC cell invasion, migration, proliferation, and EMT. Overexpression of SEMA4C reversed the inhibitory effect of miR-129–2–3p on HCC.</p></div><div><h3>Conclusions</h3><p>Overall, we discovered that through binding to SEMA4C, miR-129–2–3p regulates HCC cell proliferation, invasion, migration, and EMT.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111872"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629764","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":"MicroRNA-138 promotes the progression of multiple myeloma through targeting paired PAX5","authors":"Xiao Yan ,&nbsp;Keting Wang ,&nbsp;Cong Shi ,&nbsp;Kaihong Xu ,&nbsp;Binbin Lai ,&nbsp;Shujun Yang ,&nbsp;Lixia Sheng ,&nbsp;Ping Zhang ,&nbsp;Ying Chen ,&nbsp;Qitian Mu ,&nbsp;Guifang Ouyang","doi":"10.1016/j.mrfmmm.2024.111869","DOIUrl":"10.1016/j.mrfmmm.2024.111869","url":null,"abstract":"<div><h3>Background</h3><p>Multiple myeloma cancer stem cells (MMSC) have been considered as the leading cause of multiple myeloma (MM) drug resistance and eventual relapse, microRNAs (miRNAs) collectively participate in the progression of MM. However, the pathogenesis of miR-138 in MMSC is still not fully understood.</p></div><div><h3>Objective</h3><p>The intention of this study was to investigate the mechanism and role of miR-138 in multiple myeloma.</p></div><div><h3>Method</h3><p>Bone marrow samples and peripheral blood from patients and normal controls were collected. Use Magnet-based Cancer Stem Cell Isolation Kit to separate and extract MMSC. Real-time quantitative PCR (RT-qPCR) was carried out to determine mRNA level. Western blot was applied to detect protein levels. MTT and flow cytometry were conducted to examine the proliferation and apoptosis of MMSC. Finally, dual-luciferase reporter gene assays were performed to confirm that paired box 5 (PAX5) is a direct target for miR-138.</p></div><div><h3>Results</h3><p>Compared with normal group, the expression of miR-138 in patients was significantly up-regulated, and the expression of miR-138 was in a negative correlation with PAX5. Additionally, downregulated miR-138 facilitated the apoptosis and inhibited the proliferation of MMSC in vitro and in vivo. Downregulated miR-138 moderated the expression of PAX5, Bcl-2, Bax, and Caspase-3. PAX5 was a direct target of miR-138.</p></div><div><h3>Conclusion</h3><p>Taken together, miR-138 plays a carcinogenic role in MM, and miR-138 adjusted the proliferation and apoptosis of MMSC by targeting PAX5. miR-138 has the probability of becoming a new medicinal target for the treatment of MM.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111869"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500042","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":"Saikosaponin-d mediates FOXG1 to reverse docetaxel resistance in prostate cancer through oxidative phosphorylation","authors":"Jun Meng,&nbsp;Bo Yang,&nbsp;Chang Shu,&nbsp;Shuai Jiang","doi":"10.1016/j.mrfmmm.2024.111875","DOIUrl":"10.1016/j.mrfmmm.2024.111875","url":null,"abstract":"<div><h3>Background</h3><p>Prostate cancer (PCa), a prevalent malignancy worldwide, is frequently identified in advanced stages due to the absence of distinctive early symptoms, thereby culminating in the development of chemotherapy-induced drug resistance. Exploring novel resistance mechanisms and identifying new therapeutic agents can facilitate the advancement of more efficacious strategies for PCa treatment.</p></div><div><h3>Methods</h3><p>Bioinformatics analysis was employed to investigate the expression of FOXG1 in PCa tissues. Subsequently, qRT-PCR was utilized to validate FOXG1 mRNA expression levels in corresponding PCa cell lines. FOXG1 knockdown was performed, and cell proliferation was assessed using CCK-8 assays, while cell migration and invasion capabilities were evaluated through wound healing and Transwell assays. Western blot and Seahorse analyzer were used to measure oxidative phosphorylation (OXPHOS) levels. Additionally, to explore potential approaches to alleviate PCa drug resistance, this study assessed the impact of biologically active saikosaponin-d (SSd) on PCa malignant progression and resistance by regulating FOXG1 expression.</p></div><div><h3>Results</h3><p>FOXG1 exhibited high expression in PCa tissues and cell lines. Knockdown of FOXG1 inhibited the proliferation, migration, and invasion of PCa cells, while FOXG1 overexpression had the opposite effect and promoted OXPHOS levels. The addition of an OXPHOS inhibitor prevented this outcome. Finally, SSd was shown to suppress FOXG1 expression and reverse docetaxel resistance in PCa cells through the OXPHOS pathway.</p></div><div><h3>Conclusion</h3><p>This work demonstrated that SSd mediated FOXG1 to reverse malignant progression and docetaxel resistance in PCa through OXPHOS.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111875"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891408","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":"NTSR1 promotes epithelial-mesenchymal transition and metastasis in lung adenocarcinoma through the Wnt/β-catenin pathway","authors":"Zhihao Zhang ,&nbsp;Dongliang Zhang ,&nbsp;Kai Su ,&nbsp;Dongqiang Wu ,&nbsp;Qiqi Hu ,&nbsp;Tianying Jin ,&nbsp;Tingting Ye ,&nbsp;Rongrong Zhang","doi":"10.1016/j.mrfmmm.2024.111877","DOIUrl":"10.1016/j.mrfmmm.2024.111877","url":null,"abstract":"<div><h3>Background</h3><p>Lung adenocarcinoma (LUAD) patients are implicated in poor prognoses and increased mortality rates. Metastasis, as a leading cause of LUAD-related deaths, requires further investigation. Highly metastatic cancer cells often exhibit extensive characteristics of epithelial-mesenchymal transition (EMT). This study attempted to identify novel targets associated with LUAD metastasis and validate their specific molecular mechanisms.</p></div><div><h3>Methods</h3><p>Bioinformatics was conducted to determine NTSR1 expression in LUAD and the enriched pathways. Immunohistochemical analysis was used to assess NTSR1 expression in LUAD tissue. qRT-PCR examined expressions of NTSR1 and Wnt/β-Catenin pathway-related genes in LUAD cells. Transwell assayed cell migration and invasion. Cell adhesion experiments were conducted to evaluate cell adhesion capacity. Western blot analysis was employed to examine expression of EMT, Wnt/β-Catenin pathway, and cell adhesion markers.</p></div><div><h3>Results</h3><p>NTSR1 was upregulated in LUAD tissues and cells, and enriched in EMT pathway. Knockdown of NTSR1 reduced migration, invasion, and adhesion abilities in LUAD cells, and inhibited EMT progression and Wnt/β-Catenin pathway. Rescue experiments demonstrated that β-Catenin activator SKL2001 reversed repressive influence of NTSR1 knockdown on LUAD cell malignant phenotypes and EMT progression.</p></div><div><h3>Conclusion</h3><p>The data obtained in this study suggested that NTSR1 stimulated EMT and metastasis in LUAD via Wnt/β-Catenin pathway. This finding may provide options for overcoming LUAD metastasis.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111877"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049673","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":"CircRNA ATF6 suppresses bladder cancer cell proliferation and migration via miR-146a-5p/FLNA axis","authors":"Bing Lu ,&nbsp;Yongqiang Zhou ,&nbsp;Zheng Ma ,&nbsp;Zhenfan Wang","doi":"10.1016/j.mrfmmm.2024.111876","DOIUrl":"10.1016/j.mrfmmm.2024.111876","url":null,"abstract":"<div><h3>Background</h3><p>Bladder cancer (BCa) is the most common malignancy with increasing morbidity and mortality. Circular RNA (circRNA) ATF6 level was downregulated in BCa after GSE92675 CircRNA microarray dataset was analyzed using GEO2R. However, its function and mechanism in BCa remain largely unknown.</p></div><div><h3>Methods</h3><p>GEO2R and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to measure levels of circRNA ATF6, microRNA-146a-5p (miR-146a-5p), and filamin A (FLNA). CircRNA ATF6 stability was assessed by actinomycin D and RNase R assays, while circRNA ATF6 cellular localization was examined by FISH experiments in T24 cells. Cell counting kit-8 (CCK-8), colony formation, wound-healing, and transwell assays were used to study circRNA ATF6’s function in growth, motility, and invasion. By examining luciferase, starBase, RNA pull-down, and RNA immunoprecipitation (RIP) experiments, we anticipated and confirmed miR-146a-5p interactions with circRNA ATF6, as well as miR-146a-5p interactions with FLNA. On tumor-bearing mice, <em>in vivo</em> experiments were conducted.</p></div><div><h3>Results</h3><p>MiR-146a-5p expression in Bca was elevated, while circRNA ATF6 and FLNA were downregulated. CircRNA ATF6 showed better stability in BCa cells, with its expression primarily in the cytoplasm. Upregulating circRNA ATF6 lowered BCa cell viability, colony numbers, and invasion numbers, but broadened their migratory pattern. MiR-146a-5p was directly sponged up by circRNA ATF6, which also detrimentally affected miR-146a-5p levels in BCa. MiR-146a-5p reduced BCa FLNA expression by targeting FLNA. FLNA silencing abolished circRNA ATF6’s mitigating function in BCa cell proliferation, motility, and invasion. <em>In vivo</em>, overexpression of circRNA ATF6 significantly reduced tumor volume and weight.</p></div><div><h3>Conclusion</h3><p>CircRNA ATF6 suppresses BCa cell growth, migration and invasion through the miR-146a-5p/FLNA axis.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111876"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049675","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}