Molecular and Cellular Probes最新文献

{"title":"Honokiol inhibits human osteosarcoma MG63 cell migration by upregulating FTO and Smad6 to promote autophagy.","authors":"Jian Wu, Wenqiang Xu, Jingchi Li, Cheng Luo, Bo Chen, Luo Lin, Tianyu Huang, Tao Luo, Lin Yang, Jiexiang Yang","doi":"10.1016/j.mcp.2024.101988","DOIUrl":"10.1016/j.mcp.2024.101988","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is a common primary malignant tumor of bone, most commonly seen in children and adolescents, which has a low survival rate and is a serious threat to patients' lives. Honokiol (HKL) is the main active components of Magnolia officinalis, which have significant anti-tumor properties. The aim of this study was to observe the autophagic and migratory effects of HKL on MG63 cells and to investigate whether the mechanism of action was related to FTO and Smad6.</p><p><strong>Methods: </strong>Firstly, we cultured MG63 cells in vitro and intervened with different concentrations of HKL to detect cell activity by CCK8, apoptosis by flow cytometry, cell migration ability by scratch assay, cell invasion ability by transwell assay and MMP2, P62, LC3 I/II, FTO and Smad6 protein expression by Western blot.</p><p><strong>Results: </strong>HKL inhibited MG63 cells activity and that this effect was dose and time dependent. Although there was no significant effect on apoptosis and invasive ability, HKL could act through effects such as promoting cell autophagy and inhibiting migration. HKL increased the protein expression levels of FTO, Smad6, MMP2, LC3 I/II and P62, and this effect was reduced after silencing of Smad6.</p><p><strong>Conclusions: </strong>HKL induced autophagy and inhibited cell migration in MG63 cells by increasing the expression of FTP and Smad6. It can be seen that HKL may be a promising drug for the treatment of OS.</p>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockout of Caspase-1 Disrupts Pyroptosis and Protects Photoreceptor Cells from Photochemical Damage.","authors":"Xiaoping Yu, Jiayuan Peng, Qian Zhong, Ailin Wu, Xiaoming Deng, Yanfeng Zhu","doi":"10.1016/j.mcp.2024.101991","DOIUrl":"https://doi.org/10.1016/j.mcp.2024.101991","url":null,"abstract":"<p><strong>Aim: </strong>Retinal photochemical damage (RPD) plays a significant role in the development of various ocular diseases, with Caspase-1 being a key contributor. This study investigates the protective effects of Caspase-1 gene-mediated pyroptosis against RPD.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) associated with RPD were identified through the analysis of two expression profiles from the GEO database. Correlation analysis was used to pinpoint pyroptosis-related genes (PRGs) linked to RPD. A Caspase-1 knockout 661W cell line was generated via CRISPR-Cas9 gene editing, and single-cell colonies were screened and purified. Validation of knockout cells was performed through RT-qPCR, gene sequencing, and Western blot analysis. Comparative assays on cell proliferation, intracellular reactive oxygen species (ROS), and cytotoxicity were conducted between wild-type and Caspase-1 knockout cells under light exposure. Further RT-qPCR and Western blot experiments examined changes in the mRNA and protein levels of key pyroptosis pathway components.</p><p><strong>Results: </strong>Significant alterations in Caspase-1 expression were observed among PRGs. Homozygous Caspase-1 knockout cell lines were confirmed through RT-qPCR, genomic PCR product sequencing, and Western blot analysis. Compared to wild-type 661W cells, Caspase-1 knockout cells exhibited higher viability and proliferation rates after 24 hours of light exposure, alongside reduced LDH release. The expression of downstream pyroptosis factors at both the mRNA and protein levels was markedly decreased in the knockout group.</p><p><strong>Conclusion: </strong>CRISPR/Cas9-mediated Caspase-1 knockout enhanced the resistance of 661W cells to photochemical damage, suggesting that Caspase-1 may serve as a potential therapeutic target for RPD-related diseases.</p>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNFRSF11B promotes the progression of bladder cancer through PI3K/AKT signaling pathway","authors":"Hao Deng ,&nbsp;Jinzhuo Ning ,&nbsp;Yuan Ruan ,&nbsp;Weimin Yu ,&nbsp;Fan Cheng","doi":"10.1016/j.mcp.2024.101989","DOIUrl":"10.1016/j.mcp.2024.101989","url":null,"abstract":"<div><div>TNFRSF11B contributes to tumorigenesis in many malignancies. Nevertheless, its function and underlying tumorigenic mechanism in bladder cancer (BC) has been rare.</div><div>The clinical significance and relevant signaling pathway of TNFRSF11B in BC were assessed using bioinformatic analysis. The determination of TNFRSF11B expression was conducted in bladder tissues and BC cells. BC cells were subjected to functional experiments to evaluate their ability to proliferate, migrate, and invade. Cell apoptosis experiments were conducted. The protein levels of markers associated with epithelial-mesenchymal transition (EMT) and molecules linked to the PI3K/AKT pathway were assessed. To evaluate the effect of the PI3K/AKT pathway on TNFRSF11B, LY294002, a PI3K/AKT pathway inhibitor, was utilized. TNFRSF11B exhibited significant upregulation in both BC tissues and various cell lines. Inhibited TNFRSF11B expression impeded the growth, movement, infiltration of BC cells. Conversely, the ultimate outcome varied when TNFRSF11B was overexpressed. In vivo assay further confirmed the above results. Furthermore, TNFRSF11B promoted malignant traits by controlling the PI3K/AKT pathway. In BC, TNFRSF11B exhibits elevated expression levels and has a substantial tumor-promoting role in BC via the PI3K/AKT pathway. Importantly, TNFRSF11B may represent a valuable prognostic tumor marker for BC treatment.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559222","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":"METTL14-mediated m6A modification upregulated SOCS3 expression alleviates thyroid cancer progression by regulating the JAK2/STAT3 pathway","authors":"Ming Zhou ,&nbsp;Yaqi Zhang ,&nbsp;Qiong Zhang ,&nbsp;Yanchu Tong","doi":"10.1016/j.mcp.2024.101987","DOIUrl":"10.1016/j.mcp.2024.101987","url":null,"abstract":"<div><div>Thyroid cancer (TC) is the most common malignant tumor of the head and neck. As a common epigenetic modification in mRNAs, N6-methyladenosine (m6A) modification plays critical roles in biological process of cancers. However, m6A methyltransferase methyltransferase-like 14 (METTL14)-mediated m6A modification and its potential regulatory mechanisms in TC are not fully elucidated. In our study, we observed that METTL14 was decreased in TC tissues and cells. And upregulation of METTL14 induced apoptotic cell death and hampered cell proliferation, epithelial mesenchymal transition (EMT) and tumor growth <em>in vitro</em> and <em>in vivo</em>. Mechanistically, METTL14 increased the expression of suppressor of cytokine signaling 3 (SOCS3) through m6A methylation modification, and knockdown of SOCS3 reversed the inhibitory effect of overexpressing METTL14 on TC tumorigenesis. In addition, METTL14-mediated m6A modification of SOCS3 inactivated the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway, and in the METTL14-overexpressing TC cells, silencing SOCS3-induced upregulation of cell proliferation, EMT and suppression of apoptosis was reversed by JAK2/STAT3 inhibitor AG490 and WP1066. Together, we indicated that METTL14/m6A/SOCS3/JAK2/STAT3 axis play an important role in the progression of TC.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479163","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":"Role of microRNAs in neutrophil extracellular trap formation and prevention: Systematic narrative review.","authors":"Bashdar Mahmud Hussen, Mohammed Fatih Rasul, Goran Sedeeq Hama Faraj, Snur Rasool Abdullah, Seerwan Hamadameen Sulaiman, Hasan Pourmoshtagh, Mohammad Taheri","doi":"10.1016/j.mcp.2024.101986","DOIUrl":"10.1016/j.mcp.2024.101986","url":null,"abstract":"<p><p>Active neutrophils play a variety of roles in both innate and adaptive immune responses, and one of the most vital roles is the formation and release of neutrophil extracellular traps (NETs). NETs are created when neutrophils release their chromatin contents to get and eradicate pathogenic organisms essentially. While NET helps fight bacteria, viruses, parasites, and infections, it is also linked to asthma, atherosclerosis, and cancer metastasis. Thus, understanding the molecular mechanisms behind NETosis formation and its inhibition is crucial for developing safe and effective therapies. This systematic review aims to identify the list of miRNAs that are associated with the formation of NETosis and illustrate the mechanism of action by classifying them based on their expression site. Moreover, it summarizes the list of miRNAs that can be targeted therapeutically to reduce NETosis in various disorders. The current study entailed the searching of PubMed and Google Scholar for articles related to the research topic role of miRNAs in NETosis in all types of disorders. The search terms and phrases included \"NETs,\" \"neutrophil extracellular traps,\" \"NETosis,\" \"miRNA,\" \"miR,\" and \"micro-RNA.\" The search was limited to articles published in English since October 2024 in both databases. Following a review of 23 papers, 19 of them met the inclusion and exclusion criteria of this study. Four papers have been removed as they are duplicated or do not meet our criteria. According to the published articles till October 2024, there are 14 miRNAs involved in the molecular pathway of NETosis which are miR-155, miR-1696, miR-7, miR-223, miR-146a, miR-142a-3p, miR-3146, miR-505, miR-4512, miR-15b-5p, miR-16-5p, miR-26b-5p, miR-125a-3p and miR-378a-3p. Moreover, eight miRNAs have been identified as possible therapeutic targets for the suppression of NETosis based on in-vivo studies carried out in various organisms, which are miR-155, miR-146a, miR-1696, miR-223, miR-142a-3p, miR-3146, miR-4512, miR-16-5p. Different miRNAs that are expressed inside or outside of neutrophils can regulate and influence NETosis. Eight miRNAs have also been identified as potential therapeutic targets, which can be utilized to inhibit the molecular pathways associated with NETosis and prevent its negative effects, such as asthma, atherosclerosis, cancer metastasis, and cancer recurrence. However, further human-based research is necessary to completely understand the role of miRNAs in the development of NETosis in humans.</p>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of circRNA-mediated competing endogenous RNA network involved in the development of cervical cancer","authors":"Shaosheng Lou ,&nbsp;Wang Yang ,&nbsp;Qian Zhao ,&nbsp;Yunshan Ouyang ,&nbsp;Lingling Cao ,&nbsp;Chen Lin","doi":"10.1016/j.mcp.2024.101984","DOIUrl":"10.1016/j.mcp.2024.101984","url":null,"abstract":"<div><h3>Background</h3><div>The abnormal expression of circRNA may contribute to the progression of cervical cancer by influencing the biological processes.</div></div><div><h3>Aim</h3><div>This study aimed to identify the differentially expressed circRNAs in cervical cancer and validate the circ_0008193 ceRNA network in cervical cancer cells.</div></div><div><h3>Methods</h3><div>Using the absolute log2 value of fold change &gt;1 and <em>p</em>-value of &lt;0.05, the differentially expressed circRNAs were obtained from GSE102686 and GSE113696 from cervical cancer tissues and cervical cancer cells with the help of the GEO2R tool. Downstream miRNAs and mRNAs were predicted using relevant informatics databases. The circRNA-miRNA-mRNA interaction network was conducted with the assistance of Cytoscape. Circ_0008193-miR-182-5p-PTEN axis was validated with expression level and cell function using RT-qPCR, a dual-luciferase reporter assay, and cellular experiments.</div></div><div><h3>Results</h3><div>GSE102686 and GSE113696 databases overlapped 7 differentially expressed circRNAs and five circRNAs have the same expression pattern. Based on the literature and expression pattern, a circRNA-miRNA-mRNA network was conducted. The circ_0008193, miR-182-5p, and PTEN expression patterns were downregulation, upregulation, and downregulation, respectively. Overexpressed circ_0008193 suppressed proliferation, migration, and invasion of cervical cancer cells. MiR-182-5p diminished the inhibitory influence of circ_0008193 on cellular behaviors, while PTEN counteracted the effect of miR-182-5p.</div></div><div><h3>Conclusion</h3><div>This investigation revealed the existence of a circRNA-miRNA-mRNA network in cervical cancer, and preliminary verified the function of circ_0008193-miR-182-5p-PTEN axis in cervical cancer cells, which offers additional guidance on investigating the molecular mechanisms of cervical cancer.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299498","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":"The Prospective role of lapatinib as an adjuvant therapy in prevalent cancers: Insights from in silico analysis targeting EGFR and HER2","authors":"Behnaz Dolatabadi ,&nbsp;Maryam Peymani ,&nbsp;Leila Rouhi ,&nbsp;Ali Salehzadeh ,&nbsp;Kiavash Hushmandi ,&nbsp;Mehrdad Hashemi","doi":"10.1016/j.mcp.2024.101985","DOIUrl":"10.1016/j.mcp.2024.101985","url":null,"abstract":"<div><h3>Introduction</h3><div>Various pieces of evidence suggest an elevation in the levels of EGFR and HER2 in different cancers leading to the proliferation, invasion, and metastasis of cancer cells. In this study, we conducted a comprehensive investigation into the expression alterations of these two receptors in various cancers using in silico data. In addition, we investigated the therapeutic potential of lapatinib as an inhibitor of these receptors in various cancer types.</div></div><div><h3>Methods</h3><div>RNAseq data for prevalent cancers were downloaded from The Cancer Genome Atlas (TCGA). After initial preprocessing, expression changes of HER2, EGFR, and candidate genes—identified based on their association with EGFR and HER2 signaling pathways—were examined. Human protein atlas data were utilized to assess the protein expression of HER2 and EGFR. GSE129254 was employed to identify molecular pathways and candidate genes associated with lapatinib. The protein-protein interaction network was used to identify lapatinib-influenced hub genes. Clinical data for common cancers were used to investigate the correlation between the expression of candidate genes and patients' mortality rates by Cox regression test.</div></div><div><h3>Results</h3><div>The findings clearly indicated a significant increase in the expression levels of HER2 and EGFR in cancers such as kidney, lung, breast, bladder, pancreas, head and neck, stomach, and endometrial, both at the mRNA and protein levels (p-value &lt;0.01). Additionally, more than 30 % of samples in some cancers showed a twofold increase in HER2 or EGFR expression. The analysis of GSE129254 data revealed that lapatinib reduces the expression of numerous genes associated with cell proliferation. METTL1, LYAR, LTV1, CCND1, NOP2, and DDX21 were identified as hub genes related to the effect of lapatinib. Our results demonstrated that many hub genes exhibited elevated expression in candidate cancers, and the upregulation of some of them was correlated with poor prognosis.</div></div><div><h3>Conclusion</h3><div>Our results indicate an upregulation in the expression levels of HER2 and EGFR in certain common cancers, suggesting that lapatinib, in addition to breast cancer, could be considered for the treatment of these cancers. Furthermore, we demonstrated that some genes with increased expression in prevalent cancers and associated with poor prognosis have the potential to be modulated by lapatinib.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382179","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":"Prognostic prediction of gastric cancer based on H&E findings and machine learning pathomics","authors":"Guoda Han ,&nbsp;Xu Liu ,&nbsp;Tian Gao ,&nbsp;Lei Zhang ,&nbsp;Xiaoling Zhang ,&nbsp;Xiaonan Wei ,&nbsp;Yecheng Lin ,&nbsp;Bohong Yin","doi":"10.1016/j.mcp.2024.101983","DOIUrl":"10.1016/j.mcp.2024.101983","url":null,"abstract":"<div><h3>Aim</h3><div>In this research, we aimed to develop a model for the accurate prediction of gastric cancer based on H&amp;E findings combined with machine learning pathomics.</div></div><div><h3>Methods</h3><div>Transcriptome data, pathological images, and clinical data from 443 cases were retrieved from TCGA (The Cancer Genome Atlas Program) for survival analysis. The images were segmented using the Otsu algorithm, and features were extracted using the PyRadiomics package. Subsequently, the cases were randomly divided into a training cohort of 165 cases and a validation cohort of 69 cases. Features selected via minimum Redundancy - Maximum Relevance (mRMR)- recursive feature elimination (RFE) screening were used to train a model using the Gradient Boosting Machine (GBM) algorithm. The model's performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, and decision curves. Additionally, the correlation between the Pathomics score (PS) and immune genes was examined.</div></div><div><h3>Results</h3><div>In the multivariate analysis, heightened infiltration of activated CD4 memory T cells was strongly associated with improved overall survival (HR = 0.505, 95 % CI = 0.342–0.745, P &lt; 0.001). The pathomic model, exhibiting robust predictive capability, demonstrated impressive AUC values of 0.844 and 0.750 in both study cohorts. The Decision Curve Analysis (DCA) unequivocally underscored the model's exceptional clinical utility. In a subsequent multivariate analysis, heightened infiltration of the PS also emerged as a significant protective factor for overall survival (HR = 0.506, 95 % CI = 0.329–0.777, P = 0.002).</div></div><div><h3>Conclusion</h3><div>The pathomic model based on H&amp;E slides for predicting the infiltration degree of activated CD4 memory T cells, along with integrated bioinformatics analysis elucidating potential molecular mechanisms, offers novel prognostic indicators for the precise stratification and individualized prognosis of gastric cancer patients.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299499","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":"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":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-31","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":"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":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-14","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}