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

{"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}

{"title":"Molecular dynamics of DNA repair and carcinogen interaction: Implications for cancer initiation, progression, and therapeutic strategies","authors":"Eman Alyafeai ,&nbsp;Eskandar Qaed ,&nbsp;Haitham Saad Al-mashriqi ,&nbsp;Ahmed Almaamari ,&nbsp;Anisa H. Almansory ,&nbsp;Fatima Al Futini ,&nbsp;Marwa Sultan ,&nbsp;Zeyao Tang","doi":"10.1016/j.mrfmmm.2024.111883","DOIUrl":"10.1016/j.mrfmmm.2024.111883","url":null,"abstract":"<div><p>The integrity of the genetic material in human cells is continuously challenged by environmental agents and endogenous stresses. Among these, environmental carcinogens are pivotal in initiating complex DNA lesions that can lead to malignant transformations if not properly repaired. This review synthesizes current knowledge on the molecular dynamics of DNA repair mechanisms and their interplay with various environmental carcinogens, providing a comprehensive overview of how these interactions contribute to cancer initiation and progression. We examine key DNA repair pathways including base excision repair, nucleotide excision repair, and double-strand break repair and their regulatory networks, highlighting how defects in these pathways can exacerbate carcinogen-induced damage. Further, we discuss how understanding these molecular interactions offers novel insights into potential therapeutic strategies. This includes leveraging synthetic lethality concepts and designing targeted therapies that exploit specific DNA repair vulnerabilities in cancer cells. By integrating recent advances in molecular biology, genetics, and oncology, this review aims to illuminate the complex landscape of DNA repair and carcinogen-induced carcinogenesis, setting the stage for future research and therapeutic innovations.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111883"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167503","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":"Therapeutic potential of curcumin in autophagy modulation: Insights into the role of transcription factor EB","authors":"Shabnam Radbakhsh ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.mrfmmm.2024.111879","DOIUrl":"10.1016/j.mrfmmm.2024.111879","url":null,"abstract":"<div><p>Transcription factor EB (TFEB) is a basic Helix–Loop–Helix/Leucine Zipper (bHLHZip) class of DNA-binding proteins, which can control the expression of genes included in the autophagy–lysosomal pathway. TFEB regulates the autophagic flux by enhancing lysosome biogenesis, forming autophagosomes, and fusion with lysosomes, thereby facilitating cellular clearance of pathogenic protein structures. Curcumin is a natural polyphenolic molecule with pharmacological properties that make it a potential therapeutic candidate for a wide range of diseases. One of the important curcumin mechanisms of action includes modulation of autophagy through affecting various signaling components such as TFEB. This review discusses <em>in vitro</em> and <em>in vivo</em> evidence on the effects of curcumin on autophagy process <em>via</em> modulating TFEB activity in different disorders.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111879"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040854","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":"Transcription factor NFYA inhibits ferroptosis in lung adenocarcinoma cells by regulating PEBP1","authors":"Feng Chen,&nbsp;Tingting Xu,&nbsp;Ni Jin,&nbsp;Digeng Li,&nbsp;Yanfu Ying,&nbsp;Chen Wang","doi":"10.1016/j.mrfmmm.2024.111873","DOIUrl":"10.1016/j.mrfmmm.2024.111873","url":null,"abstract":"<div><h3>Background</h3><p>Ferroptosis is an iron-dependent programmed cell death mediated by lipid peroxidation. The purpose was to explore the molecular mechanism by which phosphatidylethanolamine-binding protein 1 (PEBP1) regulates ferroptosis in lung adenocarcinoma (LUAD), hoping to identify novel therapeutic targets for LUAD.</p></div><div><h3>Methods</h3><p>The expression, enrichment pathways and upstream transcription factors of PEBP1 were analyzed using bioinformatics tools. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) experiments were conducted to validate the interaction and binding relationship between PEBP1 and the upstream transcription factor nuclear transcription factor Y subunit α (NFYA). Quantitative reverse transcription PCR (qRT-PCR) was conducted to measure the expression levels of PEBP1 and NFYA mRNA in LUAD cells. Cell viability was detected by cell counting kit-8 assay. In addition, levels of malondialdehyde (MDA), Fe²⁺, and lipid reactive oxygen species (ROS) were assessed to evaluate ferroptosis levels in LUAD cells.</p></div><div><h3>Results</h3><p>PEBP1 was downregulated and significantly enriched in the ferroptosis signaling pathway in LUAD. Overexpression of PEBP1 suppressed cell viability remarkably, while levels of MDA, Fe²⁺, and lipid ROS were increased. Conversely, knockdown of PEBP1 produced the opposite effects. The upstream transcription factor NFYA, predicted to be involved in the regulation of PEBP1, was also upregulated in LUAD. Dual-luciferase reporter assay, ChIP, and molecular experiments revealed that NFYA transcriptionally suppressed the expression of PEBP1, and overexpression of NFYA could reverse the effects caused by PEBP1 overexpression.</p></div><div><h3>Conclusion</h3><p>PEBP1 regulated ferroptosis in LUAD, and the transcription factor NFYA inhibited ferroptosis in LUAD cells by transcriptionally downregulating PEBP1 expression.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111873"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141602398","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":"Knockdown of SDCBP induces autophagy to promote cardiomyocyte growth and angiogenesis in hypoxia/reoxygenation model","authors":"Ling Gao,&nbsp;Wanqian Liu","doi":"10.1016/j.mrfmmm.2024.111885","DOIUrl":"10.1016/j.mrfmmm.2024.111885","url":null,"abstract":"<div><h3>Objective</h3><div>Angina, myocardial infarction, and even mortality can result from myocardial ischemia (MI). Angiogenesis facilitates tissue repair, lessens cell damage, and ensures that ischemic tissues receive blood and oxygen. This study investigated the possible mechanism of syndecan-binding protein (SDCBP) on autophagy and assessed its impact on myocardial ischemia.</div></div><div><h3>Method</h3><div>A cardiac hypoxia-reoxygenation (H/R) cell model was created for this investigation. Flow cytometry, the cell counting kit-8, and Western blotting were used to measure the damage to cardiomyocytes. Western blotting and immunofluorescence were used to quantify autophagy. Furthermore, assays for tube formation, migration, and Western blotting were used to assess angiogenic capacity. Additionally, the EGFR-PI3K-Akt signaling pathway's activation was found using Western blotting.</div></div><div><h3>Result</h3><div>In the H/R-induced cardiomyocyte model, there is a rise in the expression of SDCBP. Treatment with H/R markedly boosted apoptosis and considerably decreased cell survival. H/R induction strongly inhibits autophagy, increases P62 expression, and decreases LC3II/I expression. Moreover, H/R induction dramatically reduced the ability to form tubes, migrate, and express VEGF, all of which prevented cell angiogenesis. Furthermore, EGFR-PI3K-Akt signaling pathway expression is strongly inhibited by H/R induction. considerable reduction of H/R-induced cell damage, considerable inhibition of apoptosis, promotion autophagy and angiogenesis, and activation of the EGFR-PI3K-Akt signaling pathway are all possible with SDCBP knockdown.</div></div><div><h3>Conclusion</h3><div>To summarize, this study demonstrates that via stimulating the EGFR-PI3K-Akt signaling pathway, SDCBP knockdown may mitigate the effects of H/R-induced cardiomyocyte death and encourage autophagy and blood vessel formation. A theoretical foundation for possible myocardial infarction treatment is thus provided.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111885"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561078","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}