Biotechnology and applied biochemistry最新文献

{"title":"In Silico Molecular Docking of 2-Hydroxyanthraquinone-Substituted Spiro-/Ansa Cyclotriphosphazenes: Targeting Apoptosis via Heat Shock Protein Modulation in Breast and Colon Cancer Cells.","authors":"Seda Mesci, Burak Yazgan, Gizem Demir Demirel, Tuba Yildirim, Gönül Yenilmez Çiftçi","doi":"10.1002/bab.2767","DOIUrl":"https://doi.org/10.1002/bab.2767","url":null,"abstract":"<p><p>Cancer research takes a long time and is complex. Preclinical studies prove that compounds can be potential anticancer agents and contribute to cancer studies. Overexpression of survivin may cause decreased sensitivity of anticancer agents and antiapoptotic activation through its excretion from cells via MDR. Anthraquinones and phosphazene compounds, which are among the active biological compounds and identified in many studies on cancer, come to the fore in biochemical, microbiological, and pharmacological studies. In this study, it was aimed to investigate the effect of 2-hydroxyanthraquinone-substituted spiro-/ansa cyclotriphosphazene compounds (II-VIII) on multidrug resistance, ER stress, and apoptotic cell death pathways in breast and colon cancer cells. mRNA expressions of multidrug resistance transporter, ER stress, heat shock, and apoptotic genes assessed by qPCR. Besides protein levels of apoptosis, cell cycle and related signaling pathways (CASP3, BCL-w, sTNF-R, cIAP-2, TRAILRs, IGFBPs, Survivin, XIAP, etc.) were determined by antibody membrane array method in MCF-7 and DLD-1 cell lines. To elucidate the activities of Survivin protein-related compounds, in silico-mediated molecular docking studies were evaluated. ABCs, HSPs, and GRPs gene expressions in MCF-7 and DLD-1 cells were decreased by these compounds. Besides, in gene regulations of apoptosis and signaling pathways, it was observed that the compounds induce overexpression of BAX and underexpression BCL-2. In addition, especially survivin expression was downregulated by all the compounds. It has been determined that the compounds eliminate multidrug resistance in breast and colon cancer cells, suppress HSPs and GRPs genes, and lead the cells to death, especially through the antiapoptotic pathway Survivin. These compounds can be evaluated and developed as Survivin inhibitor agents in anticancer studies.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2767"},"PeriodicalIF":3.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970847","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":"GDF10 Regulates Iron-Dependent Lipid Oxidation in Colorectal Cancer Cells Through Interaction With IGF2.","authors":"Kaobin Ouyang, Tianying Huang, Dan Xie, Hailin Xiong","doi":"10.1002/bab.2762","DOIUrl":"https://doi.org/10.1002/bab.2762","url":null,"abstract":"<p><strong>Background: </strong>This study aims to identify genes with a high likelihood of genetic variation, significant expression differences, and prognostic implications in colorectal cancer (CRC) patients. The research also seeks to investigate the role and mechanisms of key genes in CRC through the analysis of health information data and a combination of internal and external experiments.</p><p><strong>Methods: </strong>The sequence information of CRC patients was obtained from the Cancer Genome Atlas Program (TCGA) database. Key genes were identified through differential expression analysis, enrichment analysis, interaction analysis, and survival curve analysis. Subsequently, Growth and Differentiation Factor 10 (GDF10) overexpression and knockout cell models were developed to investigate the impact of GDF10 on CRC cells using assays such as CCK8, flow cytometry, Transwell, and subcutaneous tumor formation in nude mice. Mechanistically, the effects of GDF10 and IGF2 genes on autophagy, apoptosis, and ferroptosis were studied by introducing different death pathway inhibitors. Changes in reactive oxygen species (ROS), GSH, and MDA levels in cells following silencing were also assessed. Furthermore, the influence of GDF10 and its interacting protein IGF2 on ferroptosis was evaluated through ELISA and fluorescence staining.</p><p><strong>Results: </strong>The analysis of patients in the TCGA database revealed that GDF10 expression was low in microsatellite stable (MSS) type and high in microsatellite instability (MSI) type. It was found to interact with IGF2, with low expression associated with a better prognosis. Overexpression of GDF10 was shown to significantly enhance the proliferation and invasion abilities of CRC cells, whereas low expression promoted cell apoptosis. Within the pathways of autophagy, apoptosis, and ferroptosis, low expression of GDF10 primarily regulated ferroptosis in cells. This regulation involved promoting the iron-dependent lipid oxidation process by mediating binding with IGF2, leading to increased concentrations of iron ions and oxidative metabolites in cells. This process also reduced the formation of lipid droplets and inhibited tumor development.</p><p><strong>Conclusion: </strong>GDF10 plays a crucial role in regulating ferroptosis in CRC cells through mediating IGF2 interaction, suggesting it as a promising therapeutic target for CRC.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2762"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976834","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":"Selection and Identification of Two Electrogenic Bacteria and Their Performance in Wastewater Treatment.","authors":"Wen-Ting Cui, Sha-Sha Zhang, Meng Li, Qiang Zhou, Kai-Jie Cao, Pan Hu, Bo Zhang","doi":"10.1002/bab.2764","DOIUrl":"https://doi.org/10.1002/bab.2764","url":null,"abstract":"<p><p>The potential applications of microbial fuel cells (MFCs) in wastewater treatment and energy recovery have been investigated. MFCs harness the metabolic activity of microorganisms to generate electricity from organic compounds, which is highly important for preventing environmental pollution and constructing an ecological civilization. To address the safety limitations of pathogenic electrogenic bacteria in MFCs, this study isolated two novel nonpathogenic strains, Cellulosimicrobium 99-1 and Listeria innocua 5-2, from livestock samples. Their synergistic interaction boosted voltage output by 8.2% (exceeding 400 mV) compared to pure cultures while achieving 90.6% chemical oxygen demand (COD) and 74% total nitrogen removal in domestic wastewater, demonstrating dual advantages in biosecurity and treatment efficiency. This study provides experimental data and theoretical support for the application of MFC technology in environmental engineering, laying a foundation for further optimizing MFC design and improving wastewater treatment efficiency.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2764"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975850","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":"Exploration of Basidiomycetes for Anthraquinone Dyes Decolorization in Textile Wastewater.","authors":"Pragnya Paramita Sahoo, Vikas Kumar, Preeti Pallavi, Adyasha Anapurba Sahoo, Sudip Kumar Sen, Sangeeta Raut","doi":"10.1002/bab.2763","DOIUrl":"https://doi.org/10.1002/bab.2763","url":null,"abstract":"<p><p>Anthraquinone (AQ) dyes are utilized extensively in the textile industry due to their ability to fasten fabrics. The intricate and rigid structures of AQ dyes, however, prevent them from biodegradation. They also create nitrate residues, which persist as effluents in textile wastewater and harm aquatic vegetation by obstructing light from entering the water, which affects both flora and fauna. The use of bioremediation technique is most popular because it is environmentally beneficial and economical. The aim of this study was to isolate white rot fungi (WRF) for their ability to decolorize AQ dyes and their mixtures. The current study shows the decolorization of mixture of AQ dyes (MAQD), namely, Acid blue 129 (AB129), Alizarin cyanin green (ACG), and Remazol brilliant blue R (RBBR) (200 ppm) under optimized parameters: pH 7, temperature 30°C, and shaking speed 80 rpm in 24 h by using suspended fungal isolates, VS12 (93.71%) and WF2 (92.76%) isolated from decaying wood. The highest manganese peroxidase (MnP) activity (2391.77 U/mL) was found in VS12 followed by WF2 (2318.28 U/mL) in 24 h. Moreover, the study revealed that MnP is one of the causes for decolorization of MAQD, as decolorization is directly proportional to MnP activity. On the basis of morphological features and a complete sequence analysis of 18S rRNA gene and internal transcribed spacer (ITS) region, the isolates were identified as Trametes cubensis WF2 and Polyporus umbellatus VS12. This is the first report of white rot fungal isolates T. cubensis WF2 and P. umbellatus VS12 used in efficient decolorization of MAQD (AB129, ACG, RBBR).</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2763"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977133","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":"Carboxymethyl Chitosan and Chitosan as a Bioactive Delivery System: A Review.","authors":"Parinaz Sadat Alemi, Marjan Mohamadali, Samira Arabahmadi, Shiva Irani, Fereshteh Sharifi","doi":"10.1002/bab.2758","DOIUrl":"https://doi.org/10.1002/bab.2758","url":null,"abstract":"<p><p>The functionality and mechanism of bioactive agents (BA) in treating various diseases have been studied as a progressive route. Designing an effective delivery system for transferring these molecules and components is a major challenge. For that reason, a wide range of biomaterials has been introduced to deliver BA to the target tissue or cells. Chitosan (CTS) is a nontoxic, biocompatible, biodegradable, and notable point low-cost polymer, and, as a result, can be effectively utilized in the formulation of diverse delivery systems, in biomedical applications. However, CTS has some limitations, such as poor solubility in aqueous and alkaline media, rapid swelling and degradation, and consequence fast release agent. The CTS derivative carboxymethyl chitosan (CMC) is an acceptable candidate for overcoming these limitations. CMC is a high-impact grade for pharmaceutical and biomedical applications because of its nontoxic, biocompatible, biodegradable, gelation, mucoadhesive, antibacterial, and antifungal. CMC bioactivity potentials are related to carboxyl and methyl groups added through chemical modification in the CTS backbone. In this review, the physical and chemical properties of CTS and CMC have been introduced and discussed. Afterward, its biomedical applications with delivery approaches for various BA (drugs, genes, proteins), microfluidic, and cancer have been considered.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2758"},"PeriodicalIF":3.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984026","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":"Exploiting Self-Immobilized Fungi for Biovalorization of Oil Palm Sap to Organic Acids Through Repeated-Batch Fermentation.","authors":"Benjamas Chiersilp, Asma Billateh, Ketsara Sriklab, Chutima Thongsongkaew","doi":"10.1002/bab.2730","DOIUrl":"https://doi.org/10.1002/bab.2730","url":null,"abstract":"<p><p>This study focused on utilizing agricultural waste, oil palm sap (OPS) as a sole nutrient source for organic acid production by self-immobilized fungi. Among the fungi cultured in OPS, Rhizopus oryzae TISTR 3336 was selected as it could form compact and adequate-size pellets (3-5 mm) and gave the highest total acid production yield of 0.31 ± 0.02 g/g-sugar under pH control. The optimal conditions were as follows: inoculum size of 10⁶ spores/mL and shaking speed of 120 rpm. Using concentrated OPS gave higher final concentration of organic acids but reduced the production yield. The repeated-batch fermentation of OPS by self-immobilized fungi was successfully carried out for four cycles. The optimal initial sugar concentration was 40 g/L, giving the organic acid productions ranging of 19 to 35 g/L, with yields ranging of 0.47 to 0.87 g/g-sugar. This study has shown the efficient bioconversion of agricultural wastes into organic acids using self-immobilized fungi in the repeated-batch fermentation.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972021","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":"Design and Synthesis of Triazole-Based p-tert-Butylcalix[4]Arene Conjugates and Evaluation of Their Antimicrobial, Antibiofilm, and Anti-Quorum-Sensing Activities.","authors":"Alfred Ngenge Tamfu, Selahattin Bozkurt, Ozgur Ceylan","doi":"10.1002/bab.2761","DOIUrl":"https://doi.org/10.1002/bab.2761","url":null,"abstract":"<p><p>Macrocyclic calix[n]arenes have many applications, with diverse structures that can easily be functionalized either on upper or lower rims, mostly to impart solubility and improve biological activities. In this study, triazole-based p-tert-butylcalix[4]arene conjugates (AT10a and AT10b) and their p-tert-butylphenol analogs (AT10b and AT11b) were synthesized in good yields and characterized using ¹³C NMR and ¹H NMR experiments. The compounds were evaluated for their antimicrobial (AM) activity against Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, Listeria monocytogenes), Gram-negative bacteria (Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa), and fungi (Candida albicans, Candida tropicalis), and minimal/minimum inhibitory concentration (MIC) values varied from 19 to 2500 µg/mL. The AM activities of the compounds were good against most of the strains, with S. aureus, L. monocytogenes, and C. albicans being the most susceptible. The compounds inhibited violacein synthesis in Chromobacterium violaceum CV12472 and MIC and sub-MIC concentrations. AT10a and AT11a all showed 100% inhibition at MIC and 1/2 MIC concentrations, whereas compound AT10b and compound AT11b had 85.1% ± 2.1% and 90.7% ± 1.2% inhibitions at 1/2 MIC. The compounds inhibited quorum sensing (QS) against C. violaceum CV026 at MIC and 1/2 MIC, with AT11a being the most active with inhibition diameters of 18.50 ± 0.75 mm (MIC) and 11.50 ± 0.47 mm (1/2 MIC). QS inhibition indicates that the compounds could disrupt communication and coordinated behavior in bacteria. The compounds inhibited swarming and swimming motilities against P. aeruginosa PA01 at MIC and sub-MIC concentrations, implying that they can reduce spread of bacteria and cross-infections through surface colonization. The compounds showed concentration-dependent biofilm inhibition against a range of pathogenic bacteria at MIC and sub-MIC. S. aureus, L. monocytogenes, and S. typhi biofilms were most susceptible to the compounds compared to the others. Inhibition of biofilm is an indication of possible eradication of resistance in bacteria. The results suggest that triazole-based calixarene derivatives are suitable scaffolds for the development of good AMs, which could quench cell-to-cell signaling and attenuate virulence factors in bacteria.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2761"},"PeriodicalIF":3.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966264","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":"Senkyunolide I Improves Septicemia-Induced Brain Dysfunction via Regulating Nrf2 and Astrocyte Activity.","authors":"Haohao Cao, Tao Liu, Meixia Xu","doi":"10.1002/bab.2748","DOIUrl":"https://doi.org/10.1002/bab.2748","url":null,"abstract":"<p><p>Senkyunolide I (Sen I) has a protective effect on the blood-brain barrier (BBB) in rats with sepsis-associated encephalopathy (SAE). This study investigated whether Sen I regulates Nrf2 to ameliorate sepsis-induced brain dysfunction (SIBD). Sixty rats were randomly assigned into Sham group, SAE group (Model group), SAE + Sen I group (72 mg/kg, Sen I group), and SAE+ positive control group (RTA 402, Nrf2 receptor agonist, RTA 402 group), with 15 rats in each group. The cecal ligation and puncture (CLP) method was applied to induce sepsis in rats. SAE modeling was verified 6 h after operation. The drug was administered 24 h after surgery. Six rats in each group were sacrificed 24 h after administration, with brains extracted. The remaining rats would continue to be observed for their survival status until 72 h post-surgery. Brain cell apoptosis was measured using TUNEL. We detected the expression of glial fibrillary acidic protein (GFAP) by immunofluorescence, Nrf2 gene expression by RT-qPCR, and the protein expression of Nrf2, MMP-9, AQP-4, and occludin by Western blot. TNF-α and IL-1β levels were tested by ELISA, and malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) by biochemical tests. Survival rate at 72 h post-surgery, Sham group was 100%. The survival rate of the Sen I group (44.4%) and the RTA 402 group (55.6%) is significantly higher than that of the Model group (11.1%). Both Sen I and RTA 402 can improve the brain tissue damage in rats caused by sepsis, specifically by reducing apoptosis and GFAP expression, reducing TNF-α, IL-1β, and MDA levels, increasing the activity of GSH-Px, downregulating the protein expression of MMP-9 and AQP-4, and upregulating the protein expression of Nrf2 and occludin. Moreover, Sen I significantly increased the expression of Nrf2 in rat brain tissues. Sen I ameliorates SIBD in rats by regulating the expression of Nrf2 and astrocyte activation.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2748"},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971948","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":"Metolazone and Azosemide, Clinically Utilized Diuretics, Exhibit Inhibitory Activity for Glyoxalase I.","authors":"Masahiro Watanabe, Takao Toyomura, Hidenori Wake, Takashi Nishinaka, Omer Faruk Hatipoglu, Hideo Takahashi, Masahiro Nishibori, Shuji Mori","doi":"10.1002/bab.2760","DOIUrl":"https://doi.org/10.1002/bab.2760","url":null,"abstract":"<p><p>Methylglyoxal (MGO), a byproduct produced in the process of glycolysis, has cytotoxicity and forms advanced glycation endproducts (AGEs), which cause cell failure in several tissues. Because MGO is mainly removed by the action of glyoxalase I (GLO1), the activity of this enzyme contributes to the accumulation of MGO. We recently found that quinetazone, a diuretic pharmaceutical agent, has the potential to inhibit GLO1 activity. Therefore, we explored whether diuretics that have a similar structure to quinetazone inhibit GLO1. The inhibitory characteristics of diuretics with recombinant GLO1 were spectrophotometrically determined. Cell proliferation and accumulation of MGO-derived AGEs were evaluated by MTT assay and Western blotting. Among the thiazide, thiazide-like, and loop diuretics, metolazone and azosemide were found to inhibit GLO1 activity by 97% at 100 µM. Furthermore, we examined whether the substructures of these diuretics have inhibitory activity, quinazolinone or phenyltetrazole were determined to be the minimal structures of metolazone or azosemide required for inhibition of GLO1, respectively. In proximal renal tubule-like HK-2 and vascular endothelial cell-like EA.hy926 cells, these diuretics were shown to inhibit cell proliferation and induce accumulation of MGO-derived AGEs. In contrast, the substructures of these diuretics that did not affect GLO1 activity did not cause these changes. Metolazone and azosemide have inhibitory effects against GLO1. Considering that these diuretics are clinically employed as pharmaceutical agents, high or prolonged dosages may contribute to pathogenesis through GLO1 inhibition, followed by MGO and/or AGE accumulation.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2760"},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810488","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":"Low RYR2 Level Relates to Poor Prognosis of Patients With Lung Adenocarcinoma by Promoting Tumor Cell Proliferation and Inhibiting Immune Cell Infiltration.","authors":"Tao Wang, Baozhen Wang, Zhongting Lu, Tao Li","doi":"10.1002/bab.2759","DOIUrl":"https://doi.org/10.1002/bab.2759","url":null,"abstract":"<p><p>Ryanodine receptor type 2 (RYR2) is a large calcium channel that has been identified as one of the most frequently mutated genes in lung adenocarcinoma (LUAD). Despite its potential significance, the role of RYR2 in LUAD remains poorly understood. In this study, we obtained transcriptomic data (normal n = 59, tumor n = 541) from TCGA portal and RYR2 protein abundance data from cProSite, which includes 86 normal and 91 tumor samples. Additionally, we assembled a cohort of 38 patients with LUAD and collected paired tumor and adjacent non-tumor control samples. To investigate the functional impact of RYR2, we employed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis to assess cell viability and apoptosis, respectively. While mitochondria function was evaluated via measuring oxygen consumption rate. The relationship between RYR2 expression level and immune cell infiltration was analyzed by immunohistochemistry and flow cytometry analysis. Furthermore, RT-qPCR and enzyme-linked immunosorbent assay were used to quantify the expression levels of CCL14 and CXCL12. Our findings demonstrated that both the mRNA and protein levels of RYR2 were significantly downregulated in LUAD samples, and lower RYR2 levels are associated with the poor patient prognosis. Overexpression of RYR2 in A549 and H1299 cells resulted in impaired mitochondrial function, decreased cell viability, and increased apoptosis. Notably, RYR2 levels exhibited a negative correlation with tumor purity, and tumors with lower RYR2 levels showed diminished infiltration of T cells and dendritic cells. Knockdown of RYR2 in LUAD cells inhibited the production of chemokines, particularly CCL14 and CXCL12. In conclusion, our study reveals that RYR2 functions as a tumor suppressor in LUAD by inducing mitochondrial dysfunction and promoting immune cell infiltration.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2759"},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810486","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}