Molecular and Cellular Probes最新文献

{"title":"Intrahepatic cholangiocarcinoma biomarkers: Towards early detection and personalized pharmacological treatments","authors":"Maurizio Capuozzo ,&nbsp;Mariachiara Santorsola ,&nbsp;Francesco Ferrara ,&nbsp;Claudia Cinque ,&nbsp;Stefania Farace ,&nbsp;Renato Patrone ,&nbsp;Vincenza Granata ,&nbsp;Andrea Zovi ,&nbsp;Guglielmo Nasti ,&nbsp;Alessandro Ottaiano","doi":"10.1016/j.mcp.2024.101951","DOIUrl":"https://doi.org/10.1016/j.mcp.2024.101951","url":null,"abstract":"<div><p>Cholangiocarcinoma (CCA) is a rare malignancy originating from the biliary tree and is anatomically categorized as intrahepatic (iCCA), perihilar, and extrahepatic or distal. iCCA, the second most prevalent hepatobiliary cancer following hepatocellular carcinoma (HCC), constitutes 5–20 % of all liver malignancies, with an increasing incidence. The challenging nature of iCCA, combined with nonspecific symptoms, often leads to late diagnoses, resulting in unfavorable outcomes. The advanced phase of this neoplasm is difficult to treat with dismal results. Early diagnosis could significantly reduce mortality attributed to iCCA but remains an elusive goal. The identification of biomarkers specific to iCCA and their translation into clinical practice could facilitate diagnosis, monitor therapy response, and potentially reveal novel interventions and personalized medicine. In this review, we present the current landscape of biomarkers in each of these contexts. In addition to CA19.9, a widely recognized biomarker for iCCA, others such as A1BG, CYFRA 21–1, FAM19A5, MMP-7, RBAK, SSP411, TuM2-PK, WFA, <em>etc.</em>, as well as circulating tumor DNA, RNA, cells, and exosomes, are under investigation. Advancing our knowledge and monitoring of biomarkers may enable us to improve diagnosis, prognostication, and apply treatments dynamically and in a more personalized manner.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"73 ","pages":"Article 101951"},"PeriodicalIF":3.3,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000033/pdfft?md5=34a9b1954e3ab966649bc816b4de14d2&pid=1-s2.0-S0890850824000033-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139503937","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":"Platelet-derived extracellular vesicles are associated with kidney injury in patients with urosepsis","authors":"Zepeng Zhu ,&nbsp;Xiaofeng Zhu ,&nbsp;Dong Wang ,&nbsp;Xun Lu ,&nbsp;Tiancheng Jiang ,&nbsp;Lei Zhang ,&nbsp;Ming Chen ,&nbsp;Aibing Yao ,&nbsp;Shuqiu Chen","doi":"10.1016/j.mcp.2024.101949","DOIUrl":"10.1016/j.mcp.2024.101949","url":null,"abstract":"<div><h3>Background</h3><p>There is increasing evidence that platelet-derived extracellular vesicles (PEVs) may be involved in the mechanisms of inflammatory storm and organ damage in sepsis. However, there are no available studies on PEVs and renal injury in patients with urosepsis.</p></div><div><h3>Methods</h3><p>We analyzed the concentration and ratio of PEVs in plasma by flow cytometry and measured plasma IL-1β/IL-6/TNF-α/NGAL levels by ELISA. Correlation analysis was also used to examine the concentration of PEVs in relation to levels of inflammatory factors and indicators of kidney damage, as well as the severity of the disease. Finally, the receiver operating characteristic curves were produced for PEVs concentrations as a diagnosis of S-AKI/AKI.</p></div><div><h3>Results</h3><p>We found significantly higher levels of IL-1β/IL-6/TNF-α/NGAL in patients with urogenital sepsis. Furthermore, the concentrations of PEVs in plasma were significantly elevated in patients with urosepsis, especially in patients with Gram-negative bacterial infections, which were significantly and positively correlated with IL-1β/IL-6/TNF-α/NGAL levels. The area under the curve for PEVs diagnosing S-AKI and AKI was 0.746 [0.484, 1.000] and 0.943 [0.874, 1.000] respectively.</p></div><div><h3>Conclusion</h3><p>Overall, the present study suggested that PEVs may mediate the release of inflammatory mediators in patients with urosepsis and participate in the mechanism of acute kidney injury, as well as having potential as diagnostic indicators of S-AKI and AKI and as early warning indicators of the severity of patients with urosepsis.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"73 ","pages":"Article 101949"},"PeriodicalIF":3.3,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089085082400001X/pdfft?md5=1bddb040b14a76297370def6e3cf2f33&pid=1-s2.0-S089085082400001X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139433059","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":"Pancancer analysis uncovers an immunological role and prognostic value of the m6A reader IGF2BP2 in pancreatic cancer","authors":"Hui Deng ,&nbsp;Hanming Yao ,&nbsp;Shurui Zhou ,&nbsp;Chong He ,&nbsp;Yuzhou Huang ,&nbsp;Yunlong Li ,&nbsp;Hanwei Chen ,&nbsp;Jianchang Shu","doi":"10.1016/j.mcp.2023.101948","DOIUrl":"10.1016/j.mcp.2023.101948","url":null,"abstract":"<div><h3>Introduction</h3><p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant gastrointestinal tumors worldwide with a dismal prognosis and high relapse rate. PDAC is considered a “cold cancer” for which immunotherapy is not effective. Therefore, to improve the prognosis for PDAC patients, it is urgent to explore the mechanism driving its insensitivity to immunotherapy.</p></div><div><h3>Materials and methods</h3><p>We conducted pancancer analyses to test IGF2BP family expression and survival in patients with different cancers via TCGA and GETx databases. Then, we determined the immunological role and prognostic value of IGF2BP2 in vitro, in vivo and in clinical specimens.</p></div><div><h3>Results</h3><p>In the present study, we found that the m6A reader IGF2BP2 was the most clinically relevant member of the IGF2BP family for pancreatic cancer. High expression of IGF2BP2 was most associated with poor prognosis and an immunosuppressive microenvironment in PDAC. By IGF2BP2 knockdown, we found that tumor cell proliferation and invasive ability were significantly diminished. Importantly, we found that IGF2BP2 expression was closely associated with high expression of immunosuppressive molecules such as PD-L1. IGF2BP2 modulated downstream PD-L1 expression by regulating its mRNA stability via m6A methylation control, and we obtained the same verification in animal experiments and human tissue specimens.</p></div><div><h3>Conclusion</h3><p>Our study contributes to existing knowledge regarding the IGF2BP2-regulated PD-L1 signaling pathway as a potential prognostic and immune biomarker in pancreatic cancer.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"73 ","pages":"Article 101948"},"PeriodicalIF":3.3,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850823000579/pdfft?md5=be2627aed2985fa7c6a7273fcd194d0a&pid=1-s2.0-S0890850823000579-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138832645","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":"Recombinant Slit2 attenuates tracheal fibroblast activation in benign central airway obstruction by inhibiting the TGF-β1/Smad3 signaling pathway","authors":"Chunyan He ,&nbsp;Lei Gu ,&nbsp;Anmao Li ,&nbsp;Yishi Li ,&nbsp;Rui Xiao ,&nbsp;Jiaxin Liao ,&nbsp;Junhao Mu ,&nbsp;Yiling Gan ,&nbsp;Mingyu Peng ,&nbsp;Giri Mohan ,&nbsp;Wei Liu ,&nbsp;Li Xu ,&nbsp;Shuliang Guo","doi":"10.1016/j.mcp.2023.101947","DOIUrl":"10.1016/j.mcp.2023.101947","url":null,"abstract":"<div><p>Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2–roundabout guidance receptor 1 (Slit2–Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported. The study explored how the recombinant protein Slit2 functions in transforming growth factor-β1 (TGF-β1)-mediated airway fibrosis <em>in vivo</em> and <em>in vitro</em>. In this study, Slit2 expression initially increased in the tracheal granulation tissues of patients with tracheobronchial stenosis but decreased in the fibrotic tissue. In primary rat tracheal fibroblasts (RTFs), recombinant Slit2 inhibited the expression of extracellular matrices such as Timp1, α-SMA, and COL1A2, whereas recombinant TGF-β1 promoted the expression of Robo1, α-SMA, and COL1A2. Slit2 and TGF-β1 played a mutual inhibitory role in RTFs. Slit2 supplementation and Robo1 downregulation inhibited excessive extracellular matrix (ECM) deposition induced by TGF-β1 in RTFs via the TGF-β1/Smad3 pathway. Ultimately, exogenous Slit2 and Robo1 knockdown-mediated attenuation of airway fibrosis were validated in a trauma-induced rat airway obstruction model. These findings demonstrate that recombinant Slit2 alleviated pathologic tracheobronchial healing by attenuating excessive ECM deposition. Slit2–Robo1 is an attractive target for further exploring the mechanisms and treatment of benign central airway obstruction.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"73 ","pages":"Article 101947"},"PeriodicalIF":3.3,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850823000567/pdfft?md5=cce6971073619e405574862ce424cc36&pid=1-s2.0-S0890850823000567-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138832646","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":"Real-time single-base specific detection of the Haemonchus contortus S168T variant associated with levamisole resistance using loop-primer endonuclease cleavage loop-mediated isothermal amplification","authors":"Alistair Antonopoulos ,&nbsp;Owen Higgins ,&nbsp;Stephen R. Doyle ,&nbsp;David Bartley ,&nbsp;Alison Morrison ,&nbsp;Maha Mansour Shalaby ,&nbsp;Julien Reboud ,&nbsp;Eileen Devaney ,&nbsp;Terry J. Smith ,&nbsp;Roz Laing ,&nbsp;Valentina Busin","doi":"10.1016/j.mcp.2023.101946","DOIUrl":"10.1016/j.mcp.2023.101946","url":null,"abstract":"<div><p><em>Haemonchus contortus</em> is a parasitic haematophagous nematode that primarily affects small ruminants and causes significant economic loss to the global livestock industry. Treatment of haemonchosis typically relies on broad-spectrum anthelmintics, resistance to which is an important cause of treatment failure. Resistance to levamisole remains less widespread than to other major anthelmintic classes, prompting the need for more effective and accurate surveillance to maintain its efficacy. Loop-primer endonuclease cleavage loop-mediated isothermal amplification (LEC-LAMP) is a recently developed diagnostic method that facilitates multiplex target detection with single nucleotide polymorphism (SNP) specificity and portable onsite testing. In this study, we designed a new LEC-LAMP assay and applied it to detect the levamisole resistance marker S168T in <em>H. contortus</em>. We explored multiplexing probes for both the resistant S168T and the susceptible S168 alleles in a single-tube assay. We then included a generic probe to detect the <em>acr-8</em> gene in the multiplex assay, which could facilitate the quantification of both resistance markers and overall genetic material from <em>H. contortus</em> in a single step. Our results showed promising application of these technologies, demonstrating a proof-of-concept assay which is amenable to detection of resistance alleles within the parasite population, with the potential for multiplex detection, and point-of-care application enabled by lateral flow end-point detection. However, further optimisation and validation is necessary.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"73 ","pages":"Article 101946"},"PeriodicalIF":3.3,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850823000555/pdfft?md5=3c7f110f86ae3d28b26553cb6d92c8b4&pid=1-s2.0-S0890850823000555-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138742578","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":"USP5: Comprehensive insights into structure, function, biological and disease-related implications, and emerging therapeutic opportunities","authors":"Si-Ting Gao ,&nbsp;Xin Xin ,&nbsp;Zhuo-yuan Wang ,&nbsp;Yi-yang Hu ,&nbsp;Qin Feng","doi":"10.1016/j.mcp.2023.101944","DOIUrl":"https://doi.org/10.1016/j.mcp.2023.101944","url":null,"abstract":"<div><p>Ubiquitin specific protease 5 (USP5) is a vital deubiquitinating enzyme that regulates various physiological functions by removing ubiquitin chains from target proteins. This review provides an overview of the structural and functional characteristics of USP5. Additionally, we discuss the role of USP5 in regulating diverse cellular processes, including cell proliferation, apoptosis, DNA double-strand damage, methylation, heat stress, and protein quality control, by targeting different substrates. Furthermore, we describe the involvement of USP5 in several pathological conditions such as tumors, pathological pain, developmental abnormalities, inflammatory diseases, and virus infection. Finally, we introduce newly developed inhibitors of USP5. In conclusion, investigating the novel functions and substrates of USP5, elucidating the underlying mechanisms of USP5-substrate interactions, intensifying the development of inhibitors, and exploring the upstream regulatory mechanisms of USP5 in detail can provide a new theoretical basis for the treatment of various diseases, including cancer, which is a promising research direction with considerable potential. Overall, USP5 plays a critical role in regulating various physiological and pathological processes, and investigating its novel functions and regulatory mechanisms may have significant implications for the development of therapeutic strategies for cancer and other diseases.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"73 ","pages":"Article 101944"},"PeriodicalIF":3.3,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850823000531/pdfft?md5=4cb89efb6488575dc0b63e99441a4181&pid=1-s2.0-S0890850823000531-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138480194","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-486-5p inhibits the proliferation of leukemia cells and induces apoptosis through targeting FOXO1","authors":"Hui Liu,&nbsp;Zengfeng Ni,&nbsp;Lili Shi,&nbsp;Lijie Ma,&nbsp;Jianqiang Zhao","doi":"10.1016/j.mcp.2023.101943","DOIUrl":"10.1016/j.mcp.2023.101943","url":null,"abstract":"","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"72 ","pages":"Article 101943"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089085082300052X/pdfft?md5=13e0653b14da557e1826a7b0995575a9&pid=1-s2.0-S089085082300052X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296298","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":"Prenatal and postnatal genetic testing toward personalized care: The non-invasive perinatal testing","authors":"Lilla Botos ,&nbsp;Erzsébet Szatmári ,&nbsp;Gyula Richárd Nagy","doi":"10.1016/j.mcp.2023.101942","DOIUrl":"10.1016/j.mcp.2023.101942","url":null,"abstract":"<div><p>This article investigates how non-invasive prenatal testing and the incorporation of genomic sequencing into newborn screening postnatally are transforming perinatal care. They improve the accuracy of prenatal and neonatal screening, allowing for early interventions and personalized therapies. Non-invasive prenatal testing before birth and saliva-sample-based newborn genomic sequencing after birth can be collectively referred to as non-invasive perinatal testing. Non-invasive prenatal testing is particularly useful for aneuploidy, whereas performance markers worsen as DNA abnormalities shrink in size. Screening for clinically actionable diseases in childhood would be crucial to personalized medical therapy, as the postnatal period remains appropriate for screening for the great majority of monogenic disorders. While genomic data can help diagnose uncommon diseases, challenges like ethics and equity necessitate joint approaches for appropriate integration in this revolutionary journey toward personalized care.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"72 ","pages":"Article 101942"},"PeriodicalIF":3.3,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850823000518/pdfft?md5=d67dd8049ca5e47bbe120d75f0c859e3&pid=1-s2.0-S0890850823000518-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720267","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":"First trimester prediction models for small-for- gestational age and fetal growth restricted fetuses without the presence of preeclampsia","authors":"Ilona Hromadnikova ,&nbsp;Katerina Kotlabova ,&nbsp;Ladislav Krofta","doi":"10.1016/j.mcp.2023.101941","DOIUrl":"10.1016/j.mcp.2023.101941","url":null,"abstract":"&lt;div&gt;&lt;p&gt;We established efficient first trimester prediction models for small-for-gestational age (SGA) and fetal growth restriction (FGR) without the presence of preeclampsia (PE) regardless of the gestational age of the onset of the disease [early FGR occurring before 32 gestational week or late FGR occurring after 32 gestational week]. The retrospective study was performed on singleton Caucasian pregnancies (n = 6440) during the period 11/2012–3/2020. Finally, 4469 out of 6440 pregnancies had complete medical records since they delivered in the Institute for the Care of Mother and Child, Prague, Czech Republic. The study included all cases diagnosed with SGA (&lt;em&gt;n&lt;/em&gt; = 37) or FGR (n = 82) without PE, and 80 selected normal pregnancies. Four microRNAs (miR-1-3p, miR-20a-5p, miR-146a-5p, and miR-181a-5p) identified 75.68 % SGA cases at 10.0 % false positive rate (FPR). Eight microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-126-3p, miR-130b-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) identified 83.80 % SGA cases at 10.0 % FPR. The prediction model for SGA based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by assisted reproductive technology (ART), first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm]. Then 81.08 % and 89.19 % pregnancies developing SGA were identified at 10.0 % FPR in case of utilization of 4 microRNA and 8 microRNA biomarkers. Simplified prediction model for SGA based on limited number of maternal clinical characteristics (maternal age and BMI, an infertility treatment by ART, and 4 microRNAs) does not improve the detection rate of SGA (70.27 % SGA cases at 10.0 % FPR) when compared with prediction model for SGA based just on the expression profile of 4 or 8 microRNAs biomarkers. Seven microRNAs only (miR-16-5p, miR-20a-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-342-3p, and miR-574-3p) identified 42.68 % FGR cases at 10.0 % FPR (AUC 0.725). However, the combination of 10 microRNAs only (miR-16-5p, miR-20a-5p, miR-100-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-342-3p, and miR-574-3p) reached a higher discrimination power (AUC 0.774). It identified 40.24 % FGR cases at 10.0 % FPR. The prediction model for any subtype of FGR based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by ART, the parity (nulliparity), the occurrence of SGA or FGR in previous gestation, and the occurrence of any autoimmune disorder, and the presence of chronic hypertension]. Then 64.63 % and 65.85 % pregnancies destinated to develop FGR were identified at 10.0 % FPR in case of utilization of 7 microRNA biomarkers or 10 microRNA biomarkers. When other clinical variables next to those ones mentioned above such as first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algori","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"72 ","pages":"Article 101941"},"PeriodicalIF":3.3,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850823000506/pdfft?md5=63eba040e01039c69114e1721e8a7590&pid=1-s2.0-S0890850823000506-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720266","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":"Transcription factor TEAD4 facilitates glycolysis and proliferation of gastric cancer cells by activating PKMYT1","authors":"Lifen Zhan ,&nbsp;Wen Wu ,&nbsp;Qiongling Yang ,&nbsp;Huiqun Shen ,&nbsp;Limin Liu ,&nbsp;Renzhi Kang","doi":"10.1016/j.mcp.2023.101932","DOIUrl":"10.1016/j.mcp.2023.101932","url":null,"abstract":"<div><h3>Background</h3><p>Gastric cancer (GC) ranks third for cancer deaths worldwide, and glycolysis is a hallmark of several cancers, including GC. TEAD4 plays a role in establishing an oncogenic cascade in cancers, including GC. Whether TEAD4 can influence the glycolysis of GC cells remains uncovered. Hence, this study attempted to investigate the impact on glycolysis of GC cells by TEAD4.</p></div><div><h3>Methods</h3><p>By using bioinformatics analysis, differentially expressed mRNAs were screened, and downstream regulatory genes were predicted. Expression levels of TEAD4 and PKMYT1 were assessed by qRT-PCR. The binding sites between TEAD4 and PKMYT1 were predicted by the JASPAR database, meanwhile their modulatory relationship was confirmed through dual-luciferase assay and chromatin Immunoprecipitation (ChIP). Cell viability and proliferation were assayed via CCK-8 and colony formation assays. Glycolysis was measured by assaying extracellular acidification rate, oxygen consumption rate, and production of pyruvic acid, lactate, citrate, and malate. Expression levels of proteins (HK-2 and PKM2) related to glycolysis were assessed by Western blot.</p></div><div><h3>Results</h3><p>TEAD4 was upregulated in GC tissues and cells. TEAD4 knockdown substantially repressed glycolysis and proliferation of GC cells. PKMYT1, the target gene downstream of TEAD4, was identified via bioinformatics prediction, and its expression was elevated in GC. Dual-luciferase and ChIP assay validated the targeted relationship between the promoter region of PKMYT1 and TEAD4. As revealed by rescue experiments, the knockdown of TEAD4 reversed the stimulative effect on GC cell glycolysis and proliferation by forced expression of PKMYT1.</p></div><div><h3>Conclusion</h3><p>TEAD4 activated PKMYT1 to facilitate the proliferation and glycolysis of GC cells. TEAD4 and PKMYT1 may be possible therapeutic targets for GC.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"72 ","pages":"Article 101932"},"PeriodicalIF":3.3,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850823000415/pdfft?md5=749710aeec8c3235d170956e3e02cece&pid=1-s2.0-S0890850823000415-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154745","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}