Protein and Peptide Letters最新文献

{"title":"Unveiling the Potential Role of Hesperetin and Emodin as a Combination Therapy to Inhibit the Pancreatic Cancer Progression against the C-Met Gene.","authors":"Rangaraj Kaviyaprabha, Thandaserry Vasudevan Miji, Puthupparambil Shaji Sreelakshmi, Sridhar Muthusami, Palanisamy Arulselvan, Muruganantham Bharathi","doi":"10.2174/0109298665363165250225100109","DOIUrl":"https://doi.org/10.2174/0109298665363165250225100109","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic adenocarcinoma (PAAD) is one of the most prevalent cancers, and it has high death rates. Only 10% of PAAD patients can survive until 5 years. Hence, the improvement of survival rate of the patients should be improved.</p><p><strong>Aim: </strong>The present study used a computational approach to identify novel biomarkers and potentially effective small drug-like molecules in PAAD.</p><p><strong>Objective: </strong>The objective of this study was to identify the Differentially Expressed Genes (DEGs) and survival rate affecting genes (SDEGs) to single out the specific gene responsible for pancreatic cancer and predict the efficacy of interactions with hesperetin and emodin. Further, another objective was to validate the predicted efficacies using an MTT assay.</p><p><strong>Methods: </strong>The GEPIA2 database was used to analyze the TCGA-PAAD dataset and identify DEGs and SDEGs. Venn identified the commonly scattered genes between the DEGs and SDEGs. Network Analyst v3.0, CytoScape v3.10.1, and cytoHubba were used for PPI network construction and hub genes identification was described as target proteins. The PDB and PubChem were utilized to obtain the PDB structure of the target proteins and 13 phytocompounds in SDF format. Molecular docking studies were carried out and visualized by utilizing Autodock vina and Discovery Studio Visualizer v19.1.0.1828. The cytotoxicity was measured in the MiaPaCa-2 cell line after being treated with hesperetin and emodin.</p><p><strong>Results: </strong>A total of 9219 Differentially Expressed Genes (DEGs) from the TCGA-PAAD dataset were identified. Among them, 8740 and 479 genes were up and down-regulated with the statistical significance of P ≤ 0.05, respectively. Likely, 500 most survival rate affecting genes (SDEGs) in PAAD patients with a statistical significance of P ≤ 0.05 were identified. The common 137 genes were identified between these obtained DEGs and SDEGs. The survival heat map was delineated for the predicted 137 common genes. Ninety-six genes were identified as the most hazardous genes (highlighted in red). After that, the network was constructed by using protein-protein interaction (PPI) for the most hazardous 96 genes. From the constructed PPI network, the highly interacted top 10 genes were identified. The survival analysis was carried out to identify the most hazardous genes and revealed that all the identified genes significantly reduced the survival rate of the patients affected by PAAD. From that, high survival affecting 5 genes, such as CDK1, CENPE, NCAPG, KIF20A, and c-MET, were selected for further analysis. The molecular docking studies were carried out for the identified top 5 genes, with the 13 phytocompounds reviewed previously for anti-cancer activity. The molecular docking analysis revealed that the hesperetin (binding affinity (BA) = -8.0 kcal/mol; Root mean square deviation (RMSD) = 2.012 Å) and emodin (BA = -8.6 kcal/mol; RMSD = 1.605 ","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701385","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":"Plant-derived Cyclotides in Immunomodulation and their Therapeutic Potential.","authors":"Reema Mishra, Preeti Agarwal, Anshita Sharma, Meenal Mittal, Pooja Gulati, Aparajita Mohanty","doi":"10.2174/0109298665364479250214101422","DOIUrl":"https://doi.org/10.2174/0109298665364479250214101422","url":null,"abstract":"<p><p>The incidences of immune-related disorders have drastically increased in recent years across the world population. Treatment and management of these diseases, especially autoimmune disorders, are complex and challenging. Available synthetic drugs are not completely effective and also pose serious side effects for the patients. Cyclotides are a class of plant-derived cyclic peptides (28-37 amino acids) with three conserved disulfide linkages establishing a cyclic cystine knot (CCK) motif that makes them very stable biomolecules. Their inherent stability, bioavailability and membrane-penetrating capabilities render them attractive potential pharmacological agents. Studies have demonstrated that cyclotides can either enhance or suppress immune responses, making them versatile candidates for treating various immune-related disorders. Of more than 1000 cyclotides discovered to date, only up to 15 native cyclotides (e.g. kalata B1, pase and caripe cyclotides) have been screened to demonstrate their immunomodulatory activity. Of special significance is the chemically synthesised lysine mutant of kalata B1 viz. [T20K], where preclinical studies have shown promise in the treatment of the autoimmune disorder, multiple sclerosis. In vivo studies in mice models have demonstrated that daily administration of 1mg/day of [T20K] led to a significant decrease in the level of cytokine secretion, lesser demyelination (<1%) and very low inflammatory index (<0.5), in the immunized mice. Moreover, when compared with other immunosuppressive drugs (azathioprine, prednisolone, and cyclosporine A) there was a notable drop in mortality and morbidity in mice administered with [T20K]. The cyclotides, kalata B1 and MCoTI-I have also been used as scaffolds to graft bioactive peptides with immunomodulatory activity. Subsequent in vitro and in vivo studies of these grafted cyclotides have demonstrated their therapeutic ability. Keeping in view the therapeutic potential of cyclotides as immunomodulatory peptides, the present review discusses its current research scenario and implications for the future in tackling immune-related disorders.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664383","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":"Diminazene Aceturate (DIZE) Ameliorates Hypertension and Induces Anxiolytic- and Antidepressant-like Effects in TGR(mRen2)27","authors":"Laura A Costa, Flávio A G Mourão, Natalia Alenina, Michael Bader, Maria Jose Campagnole-Santos, Lucas M Kangussu","doi":"10.2174/0109298665357730250213050214","DOIUrl":"10.2174/0109298665357730250213050214","url":null,"abstract":"<p><strong>Introduction: </strong>Diminazene aceturate (DIZE) was described as an angiotensin-converting enzyme 2 (ACE2) activator. ACE2/Angiotensin-(1-7)/Mas receptor axis presents protective actions on cardiovascular diseases and plays an important modulatory role in the neurobiology of mood and anxiety disorders.</p><p><strong>Objectives: </strong>To evaluate the effects of chronic intracerebroventricular (ICV) treatment with DIZE on blood pressure, anxiety- and depression-like behaviors in hypertensive transgenic (mRen2)27 rats (TGR).</p><p><strong>Methods: </strong>Male TGR and Sprague-Dawley rats (10-12 weeks old) were subjected to chronic ICV infusion of DIZE (1.0 μg/h for 7 days). Blood pressure and heart rate were measured by tail plethysmography and anxiety- and depression-like behaviors were evaluated through elevated plus maze, marble burying and forced swim tests, respectively.</p><p><strong>Results: </strong>Treatment with DIZE induced a significant reduction in mean arterial pressure in both TGR and SD rats. A decrease in heart rate was only observed in the hypertensive animals. Additionally, treatment with DIZE attenuated the anxiety- and depression-like behaviors that were observed in TGR.</p><p><strong>Conclusion: </strong>DIZE has central anti-hypertensive, anxiolytic, and anti-depressive effects.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493446","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":"Comparative In Silico and In Vitro Studies of Novel Zinc/Tin Metal Coordinates Bearing BRCA-1 Mimetics on Wtp53 and Mtp53 Proteins.","authors":"Preeya Negi, Akey Krishna Swaroop, Anuj Kumar Singh, R Saranya, M Esakkimuthukumar, P Vasanth Raj, N Jawahar, S Jubie","doi":"10.2174/0109298665361116250121103146","DOIUrl":"https://doi.org/10.2174/0109298665361116250121103146","url":null,"abstract":"<p><strong>Purpose: </strong>This study compares the activity of BRCA-1 mimetics on WTp53 (wild-type p53 protein) and MTp53 (mutated-type p53 protein) proteins, examining the impact of TP53 mutations in breast cancer. p53 activators can be a new insight and synthesis of effective compounds for the treatment of cancer. The project contributes to the growing body of research on p53 activators and provides new insights into the design and synthesis of effective compounds for the treatment of cancer.</p><p><strong>Methods: </strong>Molecular docking predicted binding affinity values for WTp53 and MTp53. The MMGBSA of top compounds was run to get binding-free energies. The MD simulations were calculated, and six metal coordinates were synthesized. In vitro MTT-assays were performed with WTp53 (MCF-7) and R273H-MTp53 (MDA-MB-468) cell lines, comparing results with known p53 activator PRIMA-1 (p53-reactivation and induction of massive apoptosis-1).</p><p><strong>Results: </strong>The p53 activators established a three-featured (2RA, 1HBA) pharmacophore. The designed compounds had better Glide gscore compared to p53 activators PRIMA-1, PRIMA-1- MET (methylated PRIMA-1), and Tamoxifen with p53 protein (WTp53, R175H and R273H MTp53). The MM-GBSA results of top compounds showed binding free energies with R175HMTp53 (-22.24 to -75.45 kcal/mol), R273H-MTp53 (-22.8 to -36.36 kcal/mol), and WTp53 (-26.45 to -50.3 kcal/mol) compared to the p53 activator. The MD simulation of TSCO5/3KMD-MT in 100 ns indicated a stable complex when compared to TSCO5/3KMD-WT. The six metal coordinates (TSCO5-Zn, TSCO6-Zn, TSCO6-Sn, TSCO13-Zn, TSCO13-Sn, TSCO9-Sn) were synthesised. Based on in vitro results, IC50 for TSCO5-Zn (WTp53: 0.089μM, MTp53: 0.074μM) and TSCO5- Sn (WTp53: 0.092μM, MTp53: 0.073μM) have shown significant cytotoxicity.</p><p><strong>Conclusion: </strong>As compared to PRIMA-1, the designed compound TSCO5 metal coordinates have shown good in silico and in vitro activity on mutated p53 cell lines and are more potent than the p53 activator PRIMA-1.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410138","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":"Inconsistent Protein Stability Despite Pre-HECT Domain Helix: Unveiling Variability in HECT Ligases.","authors":"Çağdaş Dağ, Cansu Deniz Tozkoparan Ceylan, Cemre Sare Cansız","doi":"10.2174/0109298665362863250114075840","DOIUrl":"https://doi.org/10.2174/0109298665362863250114075840","url":null,"abstract":"<p><strong>Introduction: </strong>Ubiquitin and ubiquitin-like systems play crucial roles across a wide range of organisms, from simple to complex. Among the three enzyme-mediated post-translational modification (PTM) steps, the ligation step is the most critical. HERC5, a member of the HECT ligase family, is one of the three enzymes involved in the ISGylation system. However, the precise start points and lengths of the HECT domains in HECT ligases are still under debate.</p><p><strong>Method: </strong>Some studies suggest the inclusion of an additional N-terminal alpha helix region within the HECT domain. To investigate the structural biology of the HECT domain of HERC5, we produced and purified various lengths of the HERC5 HECT domain using different fusion proteins. This approach allowed us to explore the role of the N-terminal alpha helix in the stability of the HECT domain. Our experiments successfully produced and purified HERC5 HECT domains of different lengths with various fusion proteins.</p><p><strong>Result: </strong>The findings demonstrated that the N-terminal alpha-helix does not enhance the stability of the HECT domain. These results challenge the notion that the N-terminal alpha-helix should be generally included in the HECT domain across all HECT ligases.</p><p><strong>Conclusion: </strong>The inclusion of this region within the HECT domain may not be appropriate for generalization, as it does not contribute to stability, contrary to some previous suggestions.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415056","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":"Overexpression of HIF2α Enhances the Angiogenesis-Promoting Effect of hUC-MSC-Derived Extracellular Vesicles by Stimulating miR-146a.","authors":"Yihui Chen, Shichai Hong, Zhefeng Wang, Xiang Hong, Gang Chen, Yulong Huang, Yue Lin, Xinsheng Xie, Chenwei Lin, Weifeng Lu","doi":"10.2174/0109298665347753241028072130","DOIUrl":"10.2174/0109298665347753241028072130","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore whether excessive HIF2α can amplify the impact of human Umbilical Cord Mesenchymal Stem Cell-derived Extracellular Vesicles (hUC-MSC- EVs) on endothelial cells.</p><p><strong>Methods: </strong>In this study, we created HIF2α-overexpressing hUC-MSC-EVs and compared their pro-angiogenic effects with control EVs on Human Umbilical Vein Endothelial Cells (HUVECs). MTT assay and Edu staining were used to detect the viability and proliferation ability of HUVECs, and Transwell and Tube Formation Assays were used to detect cell migration and tube formation ability. qPCR assay was used to detect the expression of cellular angiogenic markers. Subsequently, miRNAs that might be regulated by HIF2α were predicted by bioinformatics analysis, and qPCR was used to detect the relative expression of miRNAs in HUVECs treated with hUC-MSC- EV, which over-expresses HIF2α. Subsequently, miR-146a inhibitors were used to investigate the role of miR-146a in mediating the pro-angiogenic effect of HIF2α on HUVECs by detecting cell viability, proliferation, migration, tube-forming ability, and expression of angiogenic markers. Finally, AKT/ERK phosphorylation and Spred1 expression were detected using Western blotting.</p><p><strong>Results: </strong>Our findings have indicated that overexpression of HIF2α significantly enhances the ability of hUC-MSC-EVs to stimulate proliferation, migration, and tube formation in HUVECs, as demonstrated by MTT/Edu staining, Transwell assay, and tube formation assay results, respectively. Mechanistically, excessive HIF2α has been found to induce the expression of miR-146a in HUVECs and the overexpression of a miR-146a inhibitor to negate the influence of excessive HIF2α on hUC-MSC-EV-induced activity in HUVECs.</p><p><strong>Conclusion: </strong>The overexpression of HIF2α is an effective strategy for enhancing the pro-angiogenic function of hUC-MSC-EVs.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"62-74"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732135","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":"Pro-fertility and <i>Antioxidant Potentials</i> of <i>Vigna unguiculata</i> (Cowpea) Protein Isolate and Essential Oil: An <i>In vivo</i> and <i>In silico</i> Studies.","authors":"Olugbenga Samuel Oladimeji, Olasunkanmi Kayode Awote, Nzubechi Olympian Elum","doi":"10.2174/0109298665358634241217094220","DOIUrl":"10.2174/0109298665358634241217094220","url":null,"abstract":"<p><strong>Introduction: </strong><i>Vigna unguiculata</i> (Cowpea), a legume rich in phytochemicals, has been traditionally used to improve fertility and treat various ailments. This study used <i>in-silico</i> and <i>invivo</i> methods to evaluate the effects of cowpea protein isolate and essential oil on reproductive hormonal and antioxidant indices.</p><p><strong>Methods: </strong>Forty (40) female rats were divided into eight groups (n=5). After 14 days of treatment, hormone levels (progesterone, prolactin, testosterone and estradiol) and antioxidant activities (superoxide dismutase (SOD), catalase (CAT) were assessed using biochemical kits and standard procedures. Molecular docking studies were performed using PyRx and Biovia Discovery Studio 2021. The ligands generated through gas chromatography-mass spectroscopy (GCMS) analysis of cowpea oil and the target proteins (SOD and CAT) were from downloaded PubChem and RCSB Protein Data Bank, respectively.</p><p><strong>Results: </strong>The results of this study showed that cowpea essential oil and protein isolate significantly (p<0.05) reduced plasma CAT and SOD activities while increasing their activities in the ovary and liver tissues compared to the infertile untreated group. Consistent administration of either cowpea oil or protein isolate was observed to positively regulate the hormonal indices in the infertile treated groups. Phthalic acid, 2-cyclohexyl ethyl isobutyl ester demonstrated a strong binding affinity and binding constant with SOD and CAT, which suggests that the ligands from cowpea essential oil may have antioxidant and pro-fertility properties that could be developed to treat fertility- related issues.</p><p><strong>Conclusion: </strong>Based on the results of this study, it can be concluded that <i>V. unguiculata</i> has antioxidant property, and can promote fertility, possibly through its rich embedded phytochemicals, which substantiates its traditional claim.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"111-123"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953979","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-584-5p Regulates MSMO1 to Modulate the AKT/PI3K Pathway and Inhibit Breast Cancer Progression.","authors":"Xin Li, Jie Liu, Lili He, Mi Tian, Yingying Xu, Bing Peng","doi":"10.2174/0109298665339026250114070523","DOIUrl":"10.2174/0109298665339026250114070523","url":null,"abstract":"<p><strong>Introduction: </strong>Endogenous microRNAs (miRNAs) are critical regulators of tumor progression, making their role in breast cancer an important area of investigation.</p><p><strong>Methods: </strong>This study examined the regulation of MSMO1 by miR-584-5p in breast cancer cells. Using bioinformatics and Western blotting, we confirmed MSMO1 expression in breast cancer cells and evaluated its effects on cell migration, invasion, and the AKT signaling pathway. In vivo experiments further supported these findings. The interaction between miR-584-5p and MSMO1 was validated through luciferase reporter assays, while functional studies highlighted the impact of miR-584-5p on cancer progression.</p><p><strong>Results: </strong>Our findings revealed that MSMO1 is upregulated in breast cancer, enhancing cell migration and invasion. Silencing MSMO1 diminished AKT pathway activity, and luciferase assays confirmed MSMO1 as a direct target of miR-584-5p.</p><p><strong>Conclusion: </strong>Overexpression of miR-584-5p suppressed migration and invasion of breast cancer cells. In summary, miR-584-5p is likely to modulate MSMO1 and subsequently regulate the AKT/ PI3K pathway, presenting a promising therapeutic target for breast cancer treatment.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"171-182"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415087","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":"MARVELD1 Promotes the Invasiveness in Pancreatic Adenocarcinoma through the Activation of Epithelial-to-Mesenchymal Transition.","authors":"Xianwei Luo, Zhenming Gao","doi":"10.2174/0109298665359781250114055525","DOIUrl":"10.2174/0109298665359781250114055525","url":null,"abstract":"<p><strong>Background: </strong>MARVEL domain-containing 1 (MARVELD1) has been implicated in the progression of several cancers, but its role in pancreatic adenocarcinoma (PAAD) remains poorly understood.</p><p><strong>Methods: </strong>RNA-seq data from the TCGA-PAAD and GTEx-Pancreas cohorts were analyzed to assess MARVELD1 expression. Stable MARVELD1 knockdown and overexpression were conducted in BxPC3 and PANC-1 cells. Cell viability, proliferation, migration, and invasion were evaluated using functional assays, and western blotting was employed to examine EMT-associated protein levels, including Vimentin, MMP2, MMP9, and E-cadherin. Differentially expressed genes (DEGs) between MARVELD1-high and MARVELD1-low groups were identified, and pathway enrichment analyses were performed.</p><p><strong>Results: </strong>We observed a significant increase of MARVELD1 in PAAD patient samples, with elevated MARVELD1 levels correlating with poor clinical survival. Knockdown of MARVELD1 in PAAD cells remarkably decreased cell proliferation and colony formation, while overexpression of MARVELD1 enhanced these properties. Moreover, simulated cell invasion and migration assay further suggested that MARVELD1 might contribute to PAAD cell aggressiveness. Mechanistically, MARVELD1 promoted tumor cell migration and invasion through the activation of Vimentin, MMP2, and MMP9 protein while suppressing E-cadherin. Bioinformatics analysis revealed that MARVELD1-high samples were enriched in EMT-related pathways, including TGF-β receptor signaling, actin cytoskeleton regulation, and cell adhesion.</p><p><strong>Conclusion: </strong>Taken together, our study highlights the roles of MARVELD1 in promoting tumor cell proliferation and invasion, suggesting its potential application as a prognostic and diagnostic biomarker for PAAD in the clinical context.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"224-233"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024413","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":"Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.","authors":"Minghui Hu, Yingyu Zhang, Pin Zhang, Kangbo Liu, Mengxin Zhang, Lifeng Li, Zhidan Yu, Xianwei Zhang, Wancun Zhang, Ying Xu","doi":"10.2174/0109298665338519241114103223","DOIUrl":"10.2174/0109298665338519241114103223","url":null,"abstract":"<p><p>With the emergence of the precision medicine era, targeting specific proteins has emerged as a pivotal breakthrough in tumor diagnosis and treatment. Apurinic/apyrimidinic Endonuclease 1 (APE1) is a multifunctional protein that plays a crucial role in DNA repair and cellular redox regulation. This article comprehensively explores the fundamental mechanisms of APE1 as a multifunctional enzyme in biology, with particular emphasis on its potential significance in disease diagnosis and strategies for tumor treatment. Firstly, this article meticulously analyzes the intricate biological functions of APE1 at a molecular level, establishing a solid theoretical foundation for subsequent research endeavors. In terms of diagnostic applications, the presence of APE1 can be detected in patient serum samples, biopsy tissues, and through cellular in situ testing. The precise detection methods enable changes in APE1 levels to serve as reliable biomarkers for predicting tumor occurrence, progression, and patient prognosis. Moreover, this article focuses on elucidating the potential role of APE1 in tumor treatment by exploring various inhibitors, including nucleic acid-based inhibitors and small molecule drug inhibitors categories, and revealing their unique advantages in disrupting DNA repair function and modulating oxidative-reduction activity. Finally, the article provides an outlook on future research directions for APE1 while acknowledging major technical difficulties and clinical challenges that need to be overcome despite its immense potential as a target for tumor therapy.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"18-33"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795056","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}