Molecular and Cellular Probes最新文献

{"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":"<div><p>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 (<em>n</em> = 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":null,"pages":null},"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":null,"pages":null},"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}

{"title":"KIF2C promotes clear cell renal cell carcinoma progression via activating JAK2/STAT3 signaling pathway","authors":"Hao Deng ,&nbsp;Xiaobo Gong ,&nbsp;Guanghai Ji ,&nbsp;Chenglong Li ,&nbsp;Shaoping Cheng","doi":"10.1016/j.mcp.2023.101938","DOIUrl":"10.1016/j.mcp.2023.101938","url":null,"abstract":"<div><h3>Background</h3><p>Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors that can be highly aggressive. Despite advances in the exploration of its underlying molecular biology, the clinical outcome for advanced ccRCC is still unsatisfied. Recently, more attention was paid to the functions of Kinesin family member 2C (KIF2C) in cancer progression, while the specific function of KIF2C in ccRCC has not been sufficiently elucidated. The present study aims to investigate the role of KIF2C in the progression of ccRCC and reveal potential mechanisms.</p></div><div><h3>Methods</h3><p>Expression of KIF2C in ccRCC tissues and adjacent normal tissue was compared and the association of KIF2C expression level with tumor grade, stage, and metastasis were analyzed using online web tool. Kaplan-Meier survival was performed to detect the association of KIF2C expression and patient’ prognosis. Stably cell lines with KIF2C knockdown or overexpression were constructed by lentivirus infection. CCK-8, colony formation, scratch healing, and transwell invasion assays were carried out to explore the effect of KIF2C knockdown or overexpression on the proliferation, migration, and invasion of ccRCC cells. Gene set enrichment analysis (GSEA) was conducted to reveal signaling pathways associated with KIF2C expression. The effect of KIF2C on JAK2/STAT3 signaling pathway were explored by western blot assay.</p></div><div><h3>Results</h3><p>KIF2C expression was significantly upregulated in ccRCC tissues and was higher with the increase of tumor grade, stage, and metastasis. Higher expression of KIF2C was correlated with worse overall survival and diseases free survival in ccRCC patients. Silence of KIF2C inhibited proliferation, migration, and invasion in ccRCC cells. Conversely, overexpression of KIF2C had the opposite effect. GSEA results showed that JAK/STAT signaling pathway was markedly enriched in KIF2C^high group. Pearson’ correlation revealed that KIF2C expression was significantly associated with genes in JAK2/STAT3 signaling. Western blot results showed that KIF2C knockdown decreased protein expression of p-JAK2 and p-STAT3, and KIF2C overexpression increased the phosphorylation of JAK2 and STAT3. AG490, a JAK2/STAT3 signaling inhibitor, could partly impair the tumor-promoting effects of KIF2C in ccRCC.</p></div><div><h3>Conclusion</h3><p>KIF2C expression was significantly upregulated in ccRCC and correlated with tumor grade, stage, metastasis, and patients’ prognosis. KIF2C promoted ccRCC progression via activating JAK2/STAT3 signaling pathway, and KIF2C might be a novel target in ccRCC therapy.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850823000476/pdfft?md5=cc7782b3330ab333da584f8e2593c499&pid=1-s2.0-S0890850823000476-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684187","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":"AKAP12 inhibits esophageal squamous carcinoma cell proliferation, migration, and cell cycle via the PI3K/AKT signaling pathway","authors":"Xingyi Li ,&nbsp;Hao Dong ,&nbsp;Yifan Zheng ,&nbsp;Shengguang Ding ,&nbsp;Yan Li ,&nbsp;Hefei Li ,&nbsp;HaiTao Huang ,&nbsp;Congjun Zhong ,&nbsp;Tian Xie ,&nbsp;Yiming Xu","doi":"10.1016/j.mcp.2023.101939","DOIUrl":"10.1016/j.mcp.2023.101939","url":null,"abstract":"<div><p>Esophageal squamous cell carcinoma (ESCC) consistently ranks as one of the most challenging variants of squamous cell carcinomas, primarily due to the lack of effective early detection strategies. We herein aimed to elucidate the underlying mechanisms and biological role associated with A-kinase anchoring protein 12 (AKAP12) in the context of ESCC. Bioinformatic analysis had revealed significantly lower expression level of AKAP12 in ESCC tissue samples than in their non-cancerous counterparts. To gain deeper insights into the potential role of AKAP12 in the progression of ESCC, we conducted a single-gene set enrichment analysis of AKAP12 on ESCC datasets. Our findings suggested that AKAP12 exhibits functions inhibiting cell cycle progression, tumor proliferation, and epithelial-mesenchymal transition. To further validate our findings, we subjected ESCC cell lines to AKAP12 overexpression using CRISPR/Cas9-SAM. In vitro analyses demonstrated that increased expression of AKAP12 significantly reduced cell proliferation, migration, and cell cycle progression. Simultaneously, genes associated with this biological role undergo corresponding regulatory shifts. These observations provided valuable insights into the biological role played by AKAP12 in ESCC progression. In summary, AKAP12 shows promise as a new potential biomarker for early ESCC diagnosis, offering potential advantages for subsequent therapeutic intervention and disease management.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850823000488/pdfft?md5=17d50645d999cc310f9d287832e096e1&pid=1-s2.0-S0890850823000488-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50163434","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":"Screening protective miRNAs and constructing novel lncRNAs/miRNAs/mRNAs networks and prognostic models for triple-negative breast cancer","authors":"Yuelei Zhao ,&nbsp;Yichen Song ,&nbsp;Yan Zhang ,&nbsp;Meiju Ji ,&nbsp;Peng Hou ,&nbsp;Fang Sui","doi":"10.1016/j.mcp.2023.101940","DOIUrl":"10.1016/j.mcp.2023.101940","url":null,"abstract":"<div><p>Triple-negative breast cancer (TNBC) represents 10–20 % of all breast cancer (BC) cases and is characterized by poor prognosis. Given the urgent need to improve prognostication and develop specific therapies for TNBC, the identification of new molecular targets is of great importance. MicroRNA (miRNA) has been reported as a valuable and novel molecular target in the progression of TNBC. However, the expression and function of miRNAs in different tumors are heterogeneous. Herein, we first analyzed miRNA data from The Cancer Genome Atlas (TCGA) and surprisedly found that overexpressed miRNAs were associated with poor survival in all breast cancer patients, but the overexpressed miRNAs were associated with better survival in TNBC patients. Based on the heterogeneity of miRNA expression in TNBC, we conducted further analysis using univariate Cox proportional hazard regression models and identified 17 miRNAs with prognostic potential. Subsequently, a multivariate Cox model was employed to create a 3-miRNA prognostic model for predicting overall survival in TNBC patients. The diagnostic model exhibited an area under the curve (AUC) of 0.727, and multivariable Cox regression indicated that each covariate was associated with survival. These data indicate that this model is relatively accurate and robust for risk assessment, which have a certain value for clinical application. In order to explore the network behind the overexpressed miRNAs in TNBC, we established a novel network consisting of lncRNAs, miRNAs, and mRNAs through complete transcriptome data from matched samples in the TCGA database. In this network, IRS-1 appeared to be the top hub gene. Experimental results demonstrated that miR-15b-5p and miR-148a-3p effectively target IRS-1 in vitro, shedding light on the intricate regulatory mechanisms in TNBC mediated by the heterogeneous miRNAs. Besides, miR-148a-3p significantly inhibited cell migration and viability. Overall, this study may add valuable insights into the molecular landscape of TNBC based on miRNAs and have the potential to contribute to the development of targeted therapies and improved prognostic strategies of TNBC.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089085082300049X/pdfft?md5=60279843b8ab517aefbc8ac413aa45d8&pid=1-s2.0-S089085082300049X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693439","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":"Long noncoding RNA RMRP ameliorates doxorubicin-induced apoptosis by interacting with PFN1 in a P53-Dependent manner","authors":"Juexing Li ,&nbsp;Lei Zhou ,&nbsp;Yuanliang Jiang ,&nbsp;Hailan Gao ,&nbsp;Tuersuntuoheti Maierhaba ,&nbsp;Hui Gong","doi":"10.1016/j.mcp.2023.101937","DOIUrl":"10.1016/j.mcp.2023.101937","url":null,"abstract":"<div><p>Doxorubicin (DOX) often causes acute or chronic cardiotoxicity during its application. LncRNA RMRP has been reported to be associated with several biological processes, such as cartilage-hair hypoplasia, but the relationship between RMRP and DOX-induced cardiotoxicity and chronic heart failure remains obscure. To test this hypothesis, GSE124401 and GSE149870 were processed for bioinformatics, and differentially expressed RMRP was then verified in the peripheral blood of 21 patients with heart failure compared with 7 controls. For in vitro validation, we used AC16 and HEK-293T cells. qPCR was used to detect the mRNA expression levels. The degree of apoptosis was detected by Western blot and TUNEL staining. Furthermore, the interaction between RMRP and PFN1 mRNA was verified by dual-luciferase reporter assays. In bioinformatics, RMRP showed significant downregulation, which was verified in clinical samples (p &lt; 0.001) and DOX-treated AC16 models (p &lt; 0.0001). Next, overexpression of RMRP could significantly alleviate DOX-induced apoptosis, and a potential downstream molecule of RMRP, PFN1, was also negatively associated with this change. RESCUE experiments further confirmed that PFN1 could be regulated by RMRP at both the RNA and protein levels, serving as a downstream mediator of RMRP's cardioprotective effects. This interaction was then confirmed to be a direct combination (p &lt; 0.0001). Finally, we found that overexpression of RMRP could inhibit the expression of p53 and its phosphorylation level by suppressing PFN1. In summary, RMRP could exert cardioprotective effects via the PFN1/p53 axis, holding great promise for serving as a therapeutic target and potential biomarker.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41217916","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}