Cell Biochemistry and Biophysics最新文献

{"title":"Investigating Network and Experimental Effect of Silibinin on Lipin-1 and Lipin-2 Gene Expression during Ischemia-reperfusion of the Liver in Rats.","authors":"Mahboubeh Ghanbari, Hossein Ebrahimi, Abouzar Bagheri, Abbas Khonakdar-Tarsi, Hadis Mousavi","doi":"10.1007/s12013-025-01751-0","DOIUrl":"https://doi.org/10.1007/s12013-025-01751-0","url":null,"abstract":"<p><p>This study aims to investigate the impact of silibinin (SILI) on the expression of the Lipin-1 and Lipin-2 genes during warm ischemia-reperfusion (I/R) of the liver. Network pharmacology was employed to identify potential targets of SILI in the context of liver inflammation and to elucidate the mechanism underlying the regulation of Lipin gene expression. The rats were allocated into four groups, each comprising eight individuals: vehicle group: These rats underwent a median laparotomy, and were administered normal saline. (2) SILI group: Rats in this group received 50 mg/kg of SILI after laparotomy. (3) I/R group: Rats in this group experienced I/R and were administered normal saline. (4) I/R+SILI group: In this group, rats were treated with SILI in conjunction with the I/R procedure. Western and real-time PCR were used to measure protein levels, and assess Lipin-1 and Lipin-2 gene expression. The analysis identified 18 shared targets between SILI (Severe Acute Liver Injury) and liver inflammation, linking them to 107 KEGG pathways, with the mTOR signaling pathway standing out as a critical connection to Lipin. Docking studies of targets in the mTOR signaling pathway revealed binding energies of -9.7 kcal/mol for PIK3CA and -10.4 kcal/mol for mTOR protein. Furthermore, the protein level and gene expression of Lipin-1 and Lipin-2 genes were significantly elevated during I/R compared to the vehicle group (P < 0.001). However, SILI was observed to reduce their expression during I/R (P < 0.05). The beneficial effects of SILI can be attributed to the modulation of Lipin-1 and Lipin-2 gene expression during I/R, which is likely one of the mechanisms underlying its beneficial effects during I/R.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Expression Profiling Identifies CAV1, CD44, and TFRC as Potential Diagnostic Markers and Therapeutic Targets for Multiple Myeloma.","authors":"Awais Ali, Syed Luqman Ali, Waseef Ullah, Asifullah Khan","doi":"10.1007/s12013-025-01743-0","DOIUrl":"https://doi.org/10.1007/s12013-025-01743-0","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a highly malignant hematological tumor with a low overall survival rate, making the identification of innovative prognostic markers essential due to its complex and heterogeneous nature. Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, is now recognized as crucial in tumor development and progression. Consequently, ferroptosis-related genes (FRGs) are emerging as promising therapeutic targets and prognostic indicators. However, the specific roles and predictive value of FRGs in MM still remain unclear. The current study was therefore conceived to examine the possible involvement of FRGs in MM. FRGs data was obtained from the FerrDb resource. The datasets GSE133346 and GSE166122, sourced from the Gene Expression Omnibus (GEO), provided gene expression data for both healthy and MM individuals. The differentially expressed-FRGs (DE-FRGs) were identified using the limma and DESeq2 packages in R. Functional pathways were analyzed through Gene Ontology (GO) and KEGG enrichment analyses. The miRWalk database was used for miRNA association and enrichment analysis with hub genes. Prognosis-related genes were evaluated using Kaplan-Meier survival analyses. We identified 1400 differentially expressed genes and cross-referenced them with FRGs, ultimately selecting 17 as DE-FRGs or hub genes. GO analysis revealed that the primary enriched functions of these hub genes are sister chromatid segregation, condensed chromosome centromeric region, C-C chemokine receptor activity, and C-C chemokine binding. KEGG pathway analysis showed that these overlapped genes were enriched in several pathways, including cell cycle, viral protein interaction with cytokine and cytokine receptor, as well as breast and prostate cancers involved pathways. Furthermore, significant enrichment was observed in glycolysis, gluconeogenesis, and the citrate cycle pathways based on miRNAs association with the candidate genes. The CAV1, CD44, TFRC, DPP4, and GJA1 are identified as top five significant hub DE-FRGs based on protein-protein interaction (PPI) analysis from multiple resources. Survival analysis eventually identified CAV1, CD44, and TFRC as the top-ranked DE-FRGs associated with overall survival, underscoring their crucial role in MM. This study identifies CAV1, CD44, and TFRC as key FRGs associated with the prognosis of MM, suggesting their potential as valuable prognostic markers and therapeutic targets to improve patient outcomes.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative In-Silico Analysis of Retroperitoneal Tumors in Colorectal Surgery: Advancements and Implications.","authors":"Wenqing Liu, Weida Chen, Maosheng Tang, Shibo Liu, Haichen Gao, Chengli Miao","doi":"10.1007/s12013-025-01733-2","DOIUrl":"https://doi.org/10.1007/s12013-025-01733-2","url":null,"abstract":"<p><p>Retroperitoneal tumors pose significant challenges in colorectal surgery due to their complex anatomical location, aggressive behavior, and heterogeneous nature. Traditional diagnostic and treatment methods often fall short in effectively managing these tumors. This study leverages advanced in-silico methodologies to perform a comprehensive analysis of retroperitoneal tumors associated with colorectal conditions. By integrating computational modeling and cutting-edge bioinformatics tools, we aim to enhance the understanding of tumor biology, improve diagnostic precision, and optimize surgical outcomes. Our integrative approach combines transcriptomic, and proteomic data from publicly available databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Transcriptomic analysis reveals differentially expressed genes (DEGs) that serve as potential biomarkers for early diagnosis and prognosis. Proteomic analysis highlights critical protein interaction networks and pathways involved in tumorigenesis and metastasis. Our integrative approach identifies key DEGs and constructs protein-protein interaction (PPI) networks to pinpoint critical regulatory genes, such as VWF, PF4, ITGA2B, CXCL8, and GP9, that may serve as potential biomarkers or therapeutic targets. Functional enrichment analysis reveals significant pathways involved in tumorigenesis, including cell proliferation, immune response, and DNA repair. Additionally, immune cell infiltration analysis using the CIBERSORT algorithm demonstrates an immunosuppressive tumor microenvironment characterized by increased regulatory T cells (Tregs) and M2 macrophages, which could contribute to tumor immune evasion.Future studies should focus on clinical validation of these findings and the expansion of computational models to include diverse patient populations. Through these efforts, we aim to revolutionize the management of retroperitoneal tumors in colorectal surgery, ultimately improving patient care and survival rates.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Melatonin and Bee Pollen on Hematotoxicity and Hepatorenal Toxicity Induced by Long-Term Intake of Gabapentin in Female Albino Rats.","authors":"Hanan A Okail, Mohamed F El Sayed, Mohamed A Adly, Walaa Magdy Abd Elsamei","doi":"10.1007/s12013-025-01731-4","DOIUrl":"https://doi.org/10.1007/s12013-025-01731-4","url":null,"abstract":"<p><p>Gabapentin (GBN) is an anti-seizure medication that is also used to treat nerve pain and other diseases. However, its misuse is currently a growing worry, as it may pose a significant health danger. The present study aimed to evaluate the protective effect of melatonin (MEL) and bee pollen (BP) as antioxidants against GBN-induced hematotoxicity and hepatorenal toxicity in female Albino rats. In this study, fifty-six adult female albino rats were divided into seven groups (n = 8 each), served as control, GBN, MEL, BP, MEL + GBN, BP + GBN, and MEL + BP + GBN treated groups. Results showed that oral administration of GBN resulted in a hematological toxicity as confirmed by a significant reduction in RBCs, Hb concentration, Ht%, MCV, MCH, platelets as well as altering of leukocyte profiles, WBCs, neutrophils, lymphocytes, monocytes, eosinophils and basophils. The biochemical results of liver and kidney functions showed a significant decrease in serum glucose, total protein, triglycerides, urea and uric acid. However, a significant increase in albumin, cholesterol, creatinine as well as ALP, AST, and ALT liver enzymes compared to the control was found. The oral administration of MEL and BP 12 h before GBN mostly ameliorates the altered hematological and biochemical parameters as well as hepatic and renal histopathological architecture to normal levels. In conclusion, Pre-treatment with MEL and BP, individually or together provided protection against the GBN induced changes in the blood parameters as well as hepatorenal structure and function.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphine Contributes to Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells by Blocking COX-2 Methylation via Regulating the miR-23a-3p/DNMT3A Feedback.","authors":"Jian Cui, Nina Ma, Xiaohui Li, Xuexin Chen, Junxia Zhang, Wenjuan Zhang, Hong Li","doi":"10.1007/s12013-025-01749-8","DOIUrl":"https://doi.org/10.1007/s12013-025-01749-8","url":null,"abstract":"<p><p>To investigate the effects and mechanisms of morphine on epithelial-mesenchymal transformation (EMT) in triple-negative breast cancer (TNBC). The levels of miR-23a-3p, DNMT3A, and COX-2 in tumor tissues from metastatic TNBC patients treated with morphine were assessed using qRT-PCR. Functional assays assessed morphine's impact on TNBC cell malignancy. Dual luciferase reporter and RNA pull-down assays investigated the interaction between miR-23a-3p and DNMT3A. miR-23a-3p inhibitor and DNMT3A siRNA were transfected into TNBC cells. Protein expression was analyzed by Western blot. Methylation status of miR-23a-3p and COX-2 was assessed via methylation-specific PCR. Rescue experiments were performed to research whether morphine modulates EMT in TNBC through COX-2 methylation regulation via the miR-23a-3p/DNMT3A feedback loop. The effects of morphine on TNBC in nude mice xenotransplantation were studied. In metastatic TNBC patients treated with morphine, miR-23a-3p and COX-2 expression were elevated, and DNMT3A levels were reduced. In TNBC cells, morphine enhanced migration, invasion, and EMT, and suppressed apoptosis. It upregulated miR-23a-3p and COX-2; downregulated DNMT3A; and inhibited methylation of miR-23a-3p and COX-2. miR-23a-3p directly inhibited DNMT3A expression. In morphine-treated TNBC cells, silencing DNMT3A reduced methylation of miR-23a-3p and COX-2. miR-23a-3p inhibitor suppressed migration, invasion, and EMT, and promoted apoptosis; however, these effects were reversed by DNMT3A silencing. In vivo, morphine promoted tumor EMT and metastasis in TNBC; reduced miR-23a-3p and COX-2 methylation; and decreased DNMT3A expression. Morphine accelerated EMT in TNBC by inhibiting COX-2 methylation through the miR-23a-3p/DNMT3A loop.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-518b Promotes the Tumorigenesis of Hepatocellular Carcinoma by Targeting EGR1 to Regulate PI3K/AKT/mTOR Signaling Pathway.","authors":"Xinyuan Wang, Juan Li, Jiao Nong, Xin Deng, Yiping Chen, Bing Han, Lin Zeng, Xiabing Huang","doi":"10.1007/s12013-025-01752-z","DOIUrl":"https://doi.org/10.1007/s12013-025-01752-z","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a prevalent malignancy originating from hepatocytes and is characterized by high invasiveness and fatality. Dysregulation of microRNAs (miRNAs) is frequently observed during HCC progression. This study aimed to investigate the role of miR-518b in HCC cell malignancy and tumor growth. MiR-518b expression in HCC cells was measured by RT-qPCR. The proliferative, migratory and invasive capabilities of Hep3B and SNU-387 were assessed by colony formation, wound healing and transwell assays, respectively. RNA immunoprecipitation and luciferase reporter assays were utilized to verify the binding between miR-518b and its target gene, early growth response factor 1 (EGR1). Results revealed that miR-518b was highly expressed while EGR1 was downregulated in HCC cells. Knockdown of miR-518b significantly repressed cell proliferation, migration and invasion. Moreover, miR-518b bound to 3'untranslated region of EGR1 and negatively regulated its expression in HCC cells. EGR1 knockdown counteracted the inhibitory impact of miR-518b inhibition on malignant cell behaviors. In addition, the silencing of EGR1 activated the PI3K/AKT/mTOR signaling in HCC cells, while miR-518b depletion had the opposite effect. Importantly, the suppressive impact of miR-518b on the pathway was rescued by EGR1 knockdown. In vivo experiments demonstrated that inhibition of miR-518b suppressed HCC tumor growth, reduced EGR1 and Ki67 (a proliferation marker) expression, and inactivated the PI3K/AKT/mTOR signaling. In conclusion, miR-518b promotes HCC tumorigenesis by targeting EGR1 and regulating the PI3K/AKT/mTOR signaling pathway.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANO6 Targets TMEM30A to Regulate Endoplasmic Reticulum Stress-Induced Lipid Peroxidation and Ferroptosis in Alzheimer's Cells.","authors":"Ying Wang, Penghui Li, Yonghan Liang, Dandan Wang","doi":"10.1007/s12013-025-01748-9","DOIUrl":"https://doi.org/10.1007/s12013-025-01748-9","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, and the role of ANO6 in its progression remains largely unexplored. GSE118553 database was analyzed for ANO6 expression in AD. A total of 1 μmol/L Aβ1-42 treated SH-SY5Y cells were constructed as a cell model of AD. qRT-PCR and ELISA were used to detect the expression of ANO6, GPX4, ATF6, GRP78, IREIα expression and lipid peroxidation level. Endoplasmic reticulum(ER) stress was induced by using clindamycin and lipid peroxidation indicators were detected. ANO6 was concurrently regulated in ER stress induced by clindamycin treatment. The STRING-DB database was utilized to predict potential target molecules of ANO6, while Western blot analysis was conducted to detect the expression levels of TMEM30A and evaluate the impact of ANO6-targeted TMEM30A on the protein levels within the PERK-eIF2α-ATF4-CHOP pathway. ANO6 was highly expressed in AD model, Aβ1-42 induced ANO6 enrichment in SH-SY5Y cells. ANO6 interference increased the proliferation level of AD model cells, decreased the levels of GPX4, an indicator of ferroptosis, and lipid peroxidation, and down-regulated the expression of the ER stress-related proteins ATF6, GRP78, and IREIα. Clotrimazole-induced ER stress in AD model cells showed elevated expression of ANO6. ANO6 could target and inhibit TMEM30A to affect PERK-eIF2α-ATF4-CHOP pathway activity, regulate ER stress-dependent ferroptosis, and reduce neuronal loss injury. ANO6 can target inhibition of TMEM30A affecting PERK- IF2α- ATF4- CHOP pathway activity, modulate ER stress-dependent ferroptosis-induced AD progression to reduce neuronal loss injury.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effect of Artemisinin Against Luperox Induced Oxidative Stress and Insulin Resistance via Pi3k/Akt Pathway in Zebrafish Larvae.","authors":"Kadhirmathiyan Velumani, P Sundar Rajan, Mohammed Rafi Shaik, Shaik Althaf Hussain, Baji Shaik, Ajay Guru, Praveen Kumar Issac","doi":"10.1007/s12013-025-01747-w","DOIUrl":"https://doi.org/10.1007/s12013-025-01747-w","url":null,"abstract":"<p><p>Oxidative stress plays a critical role in the development of insulin resistance (IR), a key factor in metabolic disorders such as diabetes. Plant active ingredients play a crucial role in protecting organisms from environmental stressors and have shown promising therapeutic potential against various metabolic disorders. Artemisinin (ART), a sesquiterpenoid with a lactone ring obtained from the herb Artemisia annua, exhibits promising therapeutic properties. This study investigates the potential of ART on Luperox (LUP)-induced oxidative stress and the resulting IR in zebrafish larvae, specifically investigating the involvement of the PI3K/AKT signaling pathway. Zebrafish larvae were chosen due to their high sensitivity to oxidative stress, well-characterized glucose metabolism, and genetic similarity to human metabolic pathways. They were exposed to LUP to induce oxidative stress, followed by treatment with ART. The effects were evaluated through biochemical assays, fluorescence staining and gene expression analysis. ART effectively restored key antioxidant enzymes (SOD, CAT, GSH) and mitigated oxidative stress evidenced by reduction in intercellular ROS and lipid peroxidation, as confirmed through DCFDA and DPPP staining assays. Additionally, ART improved glucose uptake and lowered blood glucose levels. Gene expression analysis further indicated increased levels of PI3K/Akt signalling components and antioxidant-related genes (NRF2, HO-1, GPx, and GSR). Our results indicate that artemisinin significantly alleviates oxidative stress by reducing ROS levels and enhancing antioxidant enzyme activity. Furthermore, artemisinin mitigates IR by restoring glucose metabolism and upregulating PI3K/AKT pathway components. These findings highlight the translational potential of plant active ingredients, particularly artemisinin, for the development of therapies targeting IR and oxidative stress-related metabolic disorders.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KPT-330, A New Candidate Drug for Targeting NOTCH1 Overexpression in T-cell Acute Lymphoblastic Leukemia, An In Vitro and Silico Study.","authors":"Fariha Naz, Saima Ejaz, Tayyaba Wali, Atiqa Nudrat, Mian Abdur Rehaman Arif, Muhammad Qandeel Waheed, Fatma Hussain, Saadiya Zia","doi":"10.1007/s12013-025-01750-1","DOIUrl":"https://doi.org/10.1007/s12013-025-01750-1","url":null,"abstract":"<p><p>B and T-lymphoid cancers usually originate from lymphoid progenitor cells. T-cell ALL, a subtype of acute lymphoblastic leukemia (ALL), arises due to unlimited and abnormal growth of blast cells. KPT-330, also known as Selinexor, prevents the transport of mRNAs and proteins from the nucleus to the cytoplasm by inhibiting the XPO1 transporter protein. The study aims to explore the NOTCH1 gene as a novel therapeutic target of KPT-330 in T-cell ALL by targeting the XPO1 protein. mRNA expression of the NOTCH1 gene was significantly elevated in T-cell ALL patients. The IC50 value of KPT330 for the Jurkat cells was determined by cell viability assay. The effect of KPT-330 on NOTCH1 gene expression in Jurkat cells was evaluated after 24, 48, and 72 h intervals. KPT-330 significantly downregulated the NOTCH1 gene expression at all time points in a dose-dependent manner. The molecular docking results revealed a binding affinity of -8.8 kcal/mol and identified GLU-140, LEU-141, and SER-144 as the potential amino acids of XPO1 forming a hydrogen bond with KPT-330. In silico analysis suggested the interaction of KPT-330 with the RNA-based NES_1 (UGUAUUAUU), NES_2 (UGUAUUUUU), and NES_3 (UUGUA) motifs in the 3' UTR of NOTCH1 mRNA resulting in NOTCH1 inhibition. Based on the results of in vitro and in silico studies, it was suggested that KPT-330 could be an ideal candidate drug for treating T-cell ALL patients with NOTCH1 overexpression.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired Cellular Cholesterol Homeostasis Decreases Tumor-Derived Exosome Load And Modulates Malignant Transformation in Cancer Cells.","authors":"Syed Sultan Beevi, Aishwarya Sudam Bhale, Vinod Kumar Verma, Radhika Chowdary Darapuneni","doi":"10.1007/s12013-025-01744-z","DOIUrl":"https://doi.org/10.1007/s12013-025-01744-z","url":null,"abstract":"<p><p>Tumor-derived exosomes (TDEs) play a crucial role in horizontally transferring oncogenic information from tumors to other sites. Cellular cholesterol homeostasis has emerged as a significant factor influencing exosomal biogenesis and cellular release. In this study, we employed U18666A to induce cholesterol accumulation within the late endosomes of MDA-MB231 cells. We assessed the capacity of exosomes derived from U18666A-treated and untreated cells to initiate malignant transformation in HEK293 cells. Exosomes were isolated and characterized from both untreated and U18666A-treated MDA-MB231 cells, and HEK293 cells. The impact of exosomes derived from untreated MDA-MB231 cells (referred to as UCE) and U18666A-treated MDA-MB231 cells (referred to as UTCE) to induce transformation on HEK293 cells was investigated. Exosomes derived from MDA-MB231 cells induced proliferation, migration, malignant transformation, and epithelial-mesenchymal transition (EMT) process in HEK293 cells. Treatment with U18666A resulted in cholesterol accumulation within late endosomes, consequently markedly reversing the EMT process in MDA-MB231 cells. This treatment diminished the content of Tumor-derived exosomes released by the cancer cells, rendering them less oncogenic. This reduction in oncogenic potential was evident as they lost the ability to induce malignant transformation in recipient HEK293 cells. Modulating cholesterol homeostasis and disrupting the supply of cholesterol to aggressive cancer cells emerges as an appealing strategy to restrain the release of Tumor-derived exosomes and subsequently mitigate their contributory role in driving cancer progression and metastasis.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}