Molecular and Cellular Probes最新文献

{"title":"Genetic switch selectively kills hepatocellular carcinoma cell based on microRNA and tissue-specific promoter","authors":"Yuan-yuan Lu ,&nbsp;Yi Li ,&nbsp;Zhi-li Chen ,&nbsp;Xiang-hua Xiong ,&nbsp;Qing-yang Wang ,&nbsp;Hao-long Dong ,&nbsp;Chen Zhu ,&nbsp;Jia-zhen Cui ,&nbsp;Ao Hu ,&nbsp;Lei Wang ,&nbsp;Na Song ,&nbsp;Gang Liu ,&nbsp;Hui-peng Chen","doi":"10.1016/j.mcp.2024.101981","DOIUrl":"10.1016/j.mcp.2024.101981","url":null,"abstract":"<div><p>The clinical treatment of hepatocellular carcinoma (HCC) is still a heavy burden worldwide. Intracellular microRNAs (miRNAs) commonly express abnormally in cancers, thus they are potential therapeutic targets for cancer treatment. miR-21 is upregulated in HCC whereas miR-122 is enriched in normal hepatocyte but downregulated in HCC. In our study, we first generated a reporter genetic switch compromising of miR-21 and miR-122 sponges as sensor, green fluorescent protein (GFP) as reporter gene and L7Ae:K-turn as regulatory element. The reporter expression was turned up in miR-21 enriched environment while turned down in miR-122 enriched environment, indicating that the reporter switch is able to respond distinctly to different miRNA environment. Furthermore, an AAT promoter, which is hepatocyte-specific, is applied to increase the specificity to hepatocyte. A killing switch with AAT promoter and an apoptosis-inducing element, Bax, in addition to miR-21 and miR-122 significantly inhibited cell viability in Huh-7 by 70 % and in HepG2 by 60 %. By contrast, cell viability was not affected in five non-HCC cells. Thus, we provide a novel feasible strategy to improve the safety of miRNA-based therapeutic agent to cancer.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"77 ","pages":"Article 101981"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000331/pdfft?md5=f411ef273941f5ad14203bbffa219364&pid=1-s2.0-S0890850824000331-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A versatile and efficient method for detecting tRNA-derived fragments","authors":"Mei Yang ,&nbsp;Yongzhen Mo ,&nbsp;Daixi Ren ,&nbsp;Yan Hu ,&nbsp;Yiting Tian ,&nbsp;Zhaoyang Zeng ,&nbsp;Wei Xiong","doi":"10.1016/j.mcp.2024.101975","DOIUrl":"10.1016/j.mcp.2024.101975","url":null,"abstract":"<div><p>Recently, it has been discovered surprisingly that tRNA can be cleaved into specific small fragments under certain conditions. Most importantly, these tRNA-derived fragments (tRFs) participate in the regulation of gene expression, playing pivotal roles in various physiological and pathological processes and thus attracting widespread attention. Detecting tRF expression in tissues and cells often involves using tRF-specific stem-loop primers for reverse transcription. However, the high specificity offered by this method limits it to transcribing only one specific tRF sequence per reaction, necessitating separate reverse transcription and qPCR steps for multiple tRFs, leading to substantially increased time and resource consumption. This becomes especially challenging in precious samples with limited RNA availability. To address these issues, there is an urgent need for a universal and cost-effective tRF identification method. This study introduces a versatile tRF detection approach based on the uniform polyadenylation of all tRFs, allowing reverse transcription with a universal oligo(dT) primer. This method enables simultaneous reverse transcription of all target tRFs in one reaction, greatly facilitating subsequent qPCR analysis. Furthermore, it demonstrates exceptional sensitivity and specificity, offering significant value in tRF-related research.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"77 ","pages":"Article 101975"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000276/pdfft?md5=3915668f148fff980843d3d63acb916c&pid=1-s2.0-S0890850824000276-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced meta-analysis on therapeutic strategies of mesenchymal derived exosome for diabetic chronic wound healing and tissue remodeling","authors":"Gunjan ,&nbsp;Himanshu ,&nbsp;Ramendra Pati Pandey ,&nbsp;Riya Mukherjee ,&nbsp;Chung-Ming Chang","doi":"10.1016/j.mcp.2024.101974","DOIUrl":"10.1016/j.mcp.2024.101974","url":null,"abstract":"<div><h3>Background</h3><p>Exosome (EXOs) are rapidly being identified as key mediators of cell-to-cell communication. They convey biologically active molecules to target cells, serve important roles in a range of physiological and pathological processes, and have enormous potential as novel therapeutic strategies.</p></div><div><h3>Methods</h3><p>Preclinical research published between 2019 and 2023 provided the study's data searched on different medline search engine, and <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> was searched for clinical data. These papers were chosen because they are relevant to the research of mesenchymal stem cell-derived exosomes (MSC-EXOs). Thematic synthesis and meta-analysis were used to perform the meta-analysis of diabetic wound healing.</p></div><div><h3>Results</h3><p>For data extraction, a total of 18 preclinical and 4 clinical trials were selected. Preclinical investigations involving EXOs across various animal wound healing models showed promising potential for treatment. Specifically, following EXO treatment, there was a notable correlation with wound closure rates, with a pooled proportion of 46 % (95 % CI: 0.34; 0.59) and τ² of 0.0593 after 3 ± 2 days, 54 % (95 % CI: 0.43; 0.65) and τ² of 0.0465 after 7 ± 2 days, and 69 % (95 % CI: 0.62; 0.76) and τ² of 0.0221 after 14 ± 2 days, with an egger's test p-value of &lt;0.01. Further investigation into heterogeneity was conducted through subgroup analysis based on the source of EXO and the animal model utilized in the study.</p></div><div><h3>Conclusions</h3><p>EXOs are proving to be viable platforms for the treatment of a wide range of disorders in clinical trials. MSC-EXOs exhibited significant diabetic wound healing capabilities across diverse outcomes including wound closure, increase angiogenesis, immunomodulatory ability and skin regeneration with its typical structure and functions.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"77 ","pages":"Article 101974"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000264/pdfft?md5=18142ca238c627bd6e07bb801809086f&pid=1-s2.0-S0890850824000264-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM47 inhibits cisplatin chemosensitivity and endoplasmic reticulum stress-induced apoptosis of ovarian cancer cells","authors":"Jiao Zhao,&nbsp;Jingru Zhang,&nbsp;Xiaojing Tong,&nbsp;Lili Zhao,&nbsp;Rong Cao","doi":"10.1016/j.mcp.2024.101978","DOIUrl":"10.1016/j.mcp.2024.101978","url":null,"abstract":"<div><p>Ovarian cancer (OC) is the fifth most common cause of death in women worldwide. Chemoresistance is a key reason for treatment failure, causing high mortality. As a member of the tripartite motif-containing (TRIM) protein family, tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers. This study investigated the impact and mechanisms of TRIM47 on cisplatin (DDP) chemosensitivity and apoptosis in OC. OC cell viability was assessed with a cell counting kit-8 assay and OC cell apoptosis was assessed using flow cytometry, caspase-3 and caspase-9 activity, and Bax and Bcl-2 expression assays while gene and protein expression were assessed using qRT–PCR and Western blot assays. The expression of TRIM47 was significantly increased in both DDP-resistant tissues from patients with OC tissues and in cancer cell lines compared with that in normal tissue or parental cell lines. The increased level of TRIM47 correlated with poor prognosis in patients with OC. Functional assays demonstrated that TRIM47 promoted DDP resistance both in vitro and in vivo. The increased viability and reduced apoptosis of OC cells induced by TRIM47 can be rescued by the endoplasmic reticulum (ER) stress–inducer tunicamycin, suggesting that TRIM47 inhibits OC cell apoptosis by suppressing ER stress. Therefore, TRIM47 may be targeted as a therapeutic strategy for DDP resistance in OC.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"77 ","pages":"Article 101978"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000306/pdfft?md5=e2e2a5f7397a5e10237b67c8397fdd1b&pid=1-s2.0-S0890850824000306-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-125b-1-3p-mediated UQCRB inhibition facilitates mitochondrial metabolism disorders in a rat cellular senescencemodel","authors":"Sha Lu,&nbsp;Cong'e Tan,&nbsp;Xue Xiao","doi":"10.1016/j.mcp.2024.101979","DOIUrl":"10.1016/j.mcp.2024.101979","url":null,"abstract":"<div><h3>Backgroud</h3><p>Cellular senescence is closely related to human aging and multiple aging-related diseases, and impaired mitochondrial energy metabolism is an important mechanism of cellular senescence. Notably, microRNA-125b-1-3p (miR-125b-1-3p) is a microRNA (miR, miRNA) that may be associated with mitochondrial energy metabolism. Ubiquinol-cytochrome c reductase binding protein (<em>UQCRB</em>) gene, predicted by bioinformatics tools to be targeted by miR-125b-1-3p, could serve as a novel diagnostic indicator and therapeutic target for cellular senescence-associated diseases, as well as a new idea for delaying aging.</p></div><div><h3>Methods</h3><p>First, the dual-luciferase reporter gene assay was used to identify <em>UQCRB</em> as a target gene of miR-125b-1-3p. Next, miRNA interference technology was conducted to verify that miR-125b-1-3p could negatively regulate the expression of <em>UQCRB</em>. Subsequently, the influence of miR-125b-1-3p on mitochondrial energy metabolism function was explored by observing the internal substances and ultrastructure of mitochondria. Further, an <em>in vitro</em> model of cellular senescence was established in rat renal tubular epithelial cells, which was characterized by detecting senescence-related proteins p16 and p21 and beta-galactosidase (β-gal) activity. Finally, the mitochondrial energy metabolism function of hydrogen peroxide (H₂O₂)-incubated cells was explored.</p></div><div><h3>Results</h3><p>The experimental results revealed that miR-125b-1-3p affected the mitochondrial energy metabolism function by inhibiting the target gene <em>UQCRB.</em> Meanwhile, the level of mitochondrial energy metabolism function in H₂O₂-incubated senescent cells was lower than that in normal cells.</p></div><div><h3>Conclusion</h3><p>In this study, we identified the target gene, <em>UQCRB</em>, of miR-125b-1-3p, and demonstrated its role in the pathway of mitochondrial energy metabolism, as well as its possible effect on cellular senescence through this pathway. The ameliorative effects on cellular senescence can be further explored in subsequent studies to provide additional options for delaying aging or treating aging-related diseases.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"77 ","pages":"Article 101979"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000318/pdfft?md5=2f164a8a41a33e01fed76a3bd1c7f0e6&pid=1-s2.0-S0890850824000318-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New potential diagnostic markers for verrucous hyperplasia and verrucous carcinoma based on RNA-sequencing data","authors":"Janghyun Kim ,&nbsp;Jee-hye Kang ,&nbsp;Myung-Giun Noh ,&nbsp;Bora Lee ,&nbsp;Yoo-Duk Choi ,&nbsp;Ok Joon Kim ,&nbsp;Young Kim","doi":"10.1016/j.mcp.2024.101980","DOIUrl":"10.1016/j.mcp.2024.101980","url":null,"abstract":"<div><p>Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma (SCC) characterized by its histological presentation as a low-grade tumor with no potential for metastasis, setting it apart from invasive SCC. However, distinguishing VC from its benign counterpart, verrucous hyperplasia (VH), is challenging due to their clinical and morphological similarities. Despite the importance of accurate diagnosis for determining treatment strategies, diagnosis for of VH and VC relied only on lesion recurrence after resection. To address this challenge, we generated RNA profiling data from tissue samples of VH and VC patients to identify novel diagnostic markers. We analyzed differentially expressed (DE) mRNA and long non-coding RNA (lncRNA) in tissue samples from VH and VC patients. Additionally, ChIP-X Enrichment Analysis 3 (ChEA3) was conducted to identify the top five transcription factors potentially regulating the expression of DE mRNAs in VH and VC. Our analysis of mRNA and lncRNA expression profiles in VH and VC provides insights into the underlying molecular characteristics of these diseases and offers potential new diagnostic markers. The identification of specific DE genes and lncRNAs may enable clinicians to more accurately differentiate between VH and VC, leading to better treatment choices.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"77 ","pages":"Article 101980"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089085082400032X/pdfft?md5=6ce56ca8e894161482b951df26676cb7&pid=1-s2.0-S089085082400032X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of the Idylla microsatellite instability test in endometrial cancer","authors":"Marta Mendiola ,&nbsp;Victoria Heredia-Soto ,&nbsp;Ignacio Ruz-Caracuel ,&nbsp;Amparo Baillo ,&nbsp;Jorge Luis Ramon-Patino ,&nbsp;Alberto Berjon ,&nbsp;Francisco Javier Escudero ,&nbsp;Alberto Pelaez-Garcia ,&nbsp;Alicia Hernandez ,&nbsp;Jaime Feliu ,&nbsp;David Hardisson ,&nbsp;Andres Redondo","doi":"10.1016/j.mcp.2024.101976","DOIUrl":"10.1016/j.mcp.2024.101976","url":null,"abstract":"<div><h3>Context</h3><p>DNA mismatch repair (MMR) deficiency (dMMR) testing is now recommended in endometrial cancer. Defect identification in the molecules participating in this pathway, or the presence of microsatellite instability, are commonly employed for this purpose. Novel methods are continuously evolving to report dMMR/microsatellite instability and to easily perform routine diagnoses.</p></div><div><h3>Objective</h3><p>The main aim of this study was to compare the concordance of the Idylla microsatellite instability test for the identification of dMMR endometrial cancer samples defined by immunohistochemistry and MMR genomic status.</p></div><div><h3>Design</h3><p>We applied the Idylla MSI test to 126 early-stage endometrial cancer cases with MMR testing by immunohistochemistry and genomic characterization (methylation in <em>MLH1</em> and sequence alterations in <em>MLH1</em>, <em>PMS2</em>, <em>MSH2</em> and <em>MSH6</em>). Individual markers and overall specific performance indicators were explored.</p></div><div><h3>Results</h3><p>The Idylla platform achieved a higher global concordance rate with MMR genomic status than with immunohistochemistry (75 % and 66 %, respectively). Sensitivity and specificity are also higher (75 % vs 66 % and 96 % vs 90 %, respectively). Clustering analysis split the patients into 2 well-differentiated clusters, the pMMR and the dMMR group, represented by MLH1/PMS2 loss and the <em>MLH1</em> methylated promoter. Overall, immunohistochemistry and MMR genomic status identified more dMMR cases than did the Idylla test, although correlations were improved with a modified Idylla test cut-off.</p></div><div><h3>Conclusions</h3><p>Performance of the Idylla test was better correlated with MMR genomic status than MMR immunohistochemistry status, which improved with a modified test cut-off. Further studies are needed to confirm the cut-off accuracy.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"77 ","pages":"Article 101976"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000288/pdfft?md5=6e130c00b8c26414f85101ba16d31a20&pid=1-s2.0-S0890850824000288-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of local anesthetic-induced heart toxicity using human induced pluripotent stem cell-derived cardiomyocytes","authors":"Ting Jiang ,&nbsp;Chao Ma ,&nbsp;Zitong Wang ,&nbsp;Yi Miao","doi":"10.1016/j.mcp.2024.101965","DOIUrl":"10.1016/j.mcp.2024.101965","url":null,"abstract":"<div><p>Local anesthetic (LA) cardiotoxicity is one of the main health problems in anesthesiology and pain management. This study reviewed the reported LA-induced cardiac toxicity types, risk factors, management, and mechanisms, with attention to the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in heart toxicity research. Important scientific databases were searched to find relevant articles. We briefly assessed the reported cardiotoxic effects of different types of LA drugs, including ester- and amide-linked LA agents. Furthermore, cardiotoxic effects and clinical manifestations, strategies for preventing and managing LA-induced cardiotoxic effects, pharmacokinetics, pharmacodynamics, and sodium channel dynamics regarding individual variability and genetic influences were discussed in this review. The applications and importance of hiPSC-CMs cellular model for evaluating the cardiotoxic effects of LA drugs were discussed in detail. This review also explored hiPSC-CMs' potential in risk assessment, drug screening, and developing targeted therapies. The main mechanisms underlying LA-induced cardiotoxicity included perturbation in sodium channels, ROS production, and disorders in the immune system response due to the presence of LA drugs. Furthermore, drug-specific characteristics including pharmacokinetics and pharmacodynamics are important determinants after LA drug injection. In addition, individual patient factors such as age, comorbidities, and genetic variability emphasize the need for a personalized approach to mitigate risks and enhance patient safety. The strategies outlined for the prevention and management of LA cardiotoxicity underscore the importance of careful dosing, continuous monitoring, and the immediate availability of resuscitation equipment. This comprehensive review can be used to guide future investigations into better understanding LA cardiac toxicities and improving patient safety.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101965"},"PeriodicalIF":3.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000173/pdfft?md5=1cb3acb73e52161bab43535f6fb19949&pid=1-s2.0-S0890850824000173-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dual-labeling molecule for efficient drug discovery of mitochondrial-lysosomal interactions","authors":"Jinfang Wu ,&nbsp;Xiaolei Wang ,&nbsp;Xiang Li ,&nbsp;Zixuan Zhu ,&nbsp;Zhongcheng Cui ,&nbsp;Tao Zhang ,&nbsp;Weiwei Zou ,&nbsp;Guanying Han","doi":"10.1016/j.mcp.2024.101968","DOIUrl":"10.1016/j.mcp.2024.101968","url":null,"abstract":"<div><p>The close association between organelle interactions, such as mitochondrial–lysosomal interactions, and various diseases, including tumors, remains a challenge for drug discovering and identification. Conventional evaluation methods are often complex and multistep labeling procedures often generate false positives, such as cell damage. To overcome these limitations, we employed a single dual-color reporting molecule called Coupa, which labels mitochondria and lysosomes as blue and red, respectively. This facilitates the evaluation and discovering of drugs targeting mitochondria–lysosome contact (MLC). Using Coupa, we validated the effectiveness of various known antitumor drugs in intervening MLC by assessing their effect on key aspects, such as status, localization, and quantity. This provides evidence for the accuracy and applicability of our dual-color reporting molecule. Notably, we observed that several structural isomers of drugs, including Urolithin (A/B/C), exhibited distinct effects on MLC. In addition, Verteporfin and TEAD were found to induce anti-tumor effects by controlling MLC at the organelle level, suggesting a potential new mechanism of action. Collectively, Coupa offers a novel scientific tool for discovering drugs that target mitochondrial–lysosomal interactions. It not only distinguished the differential effects of structurally similar drugs on the same target, but also reveals new mechanisms underlying the reported antitumor properties of existing drugs. Ultimately, our findings contribute to the advancement of drug discovery and provide valuable insights into the complex interactions between organelles in a disease context.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101968"},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000203/pdfft?md5=7b6d935625207b45235175c549e214bc&pid=1-s2.0-S0890850824000203-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of ZIC2 on immune infiltration and ceRNA axis regulation in lung adenocarcinoma via bioinformatics and experimental studies","authors":"Hongjie Huo,&nbsp;Yu Feng,&nbsp;Qiong Tang","doi":"10.1016/j.mcp.2024.101971","DOIUrl":"10.1016/j.mcp.2024.101971","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to conclude the effect and mechanism of ZIC2 on immune infiltration in lung adenocarcinoma (LUAD).</p></div><div><h3>Methods</h3><p>Expression of ZIC2 in several kinds of normal tissues of TCGA data was analyzed and its correlation with the baseline characteristic of LUAD patients were analyzed. The immune infiltration analysis of LUAD patients was performed by CIBERSORT algorithm. The correlation analysis between ZIC2 and immune cell composition was performed. Additionally, the potential upstream regulatory mechanisms of ZIC2 were predicted to identify the possible miRNAs and lncRNAs that regulated ZIC2 in LUAD. <em>In vitro</em> and <em>in vivo</em> experiments were also conducted to confirm the potential effect of ZIC2 on cell proliferation and invasion ability of LUAD cells.</p></div><div><h3>Results</h3><p>ZIC2 expression was decreased in various normal tissues, but increased in multiple tumors, including LUAD, and correlated with the prognosis of LUAD patients. Enrichment by GO and KEGG suggested the possible association of ZIC2 with cell cycle and p53 signal pathway. ZIC2 expression was significantly correlated with T cells CD4 memory resting, Macrophages M1, and plasma cells, indicating that dysregulated ZIC2 expression in LUAD may directly influence immune infiltration. ZIC2 might be regulated by several different lncRNA-mediated ceRNA mechanisms. <em>In vitro</em> experiments validated the promotive effect of ZIC2 on cell viability and invasion ability of LUAD cells. In vivo experiments validated ZIC2 can accelerate tumor growth in nude mouse.</p></div><div><h3>Conclusion</h3><p>ZIC2 regulated by different lncRNA-mediated ceRNA mechanisms may play a critical regulatory role in LUAD through mediating the composition of immune cells in tumor microenvironment.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101971"},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000239/pdfft?md5=afb0aacc5967722a8539bb9384128c97&pid=1-s2.0-S0890850824000239-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}