{"title":"N6-Methyladenosine Modification of PERP by RBM15 Enhances the Tumorigenesis of Lung Adenocarcinoma via p53 Signaling Pathway.","authors":"Ruiying Li, Xiaochuang Xia, Wenping Chen, Hongmin Wang, Lunda Feng, Zhouyi Wang","doi":"10.1007/s12033-024-01323-2","DOIUrl":"https://doi.org/10.1007/s12033-024-01323-2","url":null,"abstract":"<p><p>The promotive effect of P53 apoptosis effector related to PMP-22 (PERP) on lung adenocarcinoma (LUAD) has been confirmed. However, the N6-methyladenosine (m6A) modification of PERP to regulate LUAD progression have not been revealed. Bioinformatic analysis predicted the mechanism of PERP interacting with RBM15 and p53 pathway using GEPIA and The Cancer Genome Atlas (TCGA) databases. The qRT-PCR, cell function experiments, and western blotting were applied to further confirm the function and mechanism of PERP and RBM15 in LUAD cells. Methylated RNA immunoprecipitation (MeRIP) and mRNA stability assays were used to reveal the interaction between PERP and RBM15 in LUAD cells. PERP with high expression in LUAD showed the poor survival. Silencing PERP prevented LUAD cells to proliferate, migrate, and invade via activating p53 pathway, whereas overexpressing PERP showed the opposite effect on LUAD cells. Mechanistically, RBM15 overexpression could promote PERP m6A modification to enhance the PERP mRNA stability. In addition, RBM15 overexpression leading to LUAD cell malignancy was reversed by PERP knockdown. This study reveals that the m<sup>6</sup>A modification of PERP regulated by RBM15 enhances the tumorigenesis of LUAD by inhibiting the p53 signaling pathway, which may provide novel insights into the LUAD mechanism.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jizu Ling, BoWen Li, XinHui Yuan, WenKai Yang, KeYang Sun
{"title":"Intermittent Hypoxia Impairs Cognitive Function and Promotes Mitophagy and Lysophagy in Obstructive Sleep Apnea-Hypopnea Syndrome Rat Model.","authors":"Jizu Ling, BoWen Li, XinHui Yuan, WenKai Yang, KeYang Sun","doi":"10.1007/s12033-024-01319-y","DOIUrl":"https://doi.org/10.1007/s12033-024-01319-y","url":null,"abstract":"<p><p>Autophagy regulates intermittent hypoxia (IH)-induced obstructive sleep apnea-hypopnea syndrome (OSAHS). We investigated the effects of IH and its withdrawal on cognitive function, autophagy, and lysophagy in OSAHS. An OSAHS rat model was established, and rats were divided into five groups: normoxia control, IH-4w (4-week IH), IH-6w (6-week IH), IH-8w (8-week IH), and IH-8w + 4w (8-week IH and 4-week normoxia). The cognitive behavior; mitochondrial and lysosomal morphology of the hippocampal tissue; mitochondrial respiratory function, permeability, and membrane potential; lysosomal function; autophagy- and lysophagy-related protein levels; and hypoxia-associated autophagy gene expression in rats were assessed. The cognitive function of rats in the IH-4w, IH-6w, and IH-8w groups was significantly impaired. In IH-8w cells, mitochondrial function was damaged with swollen morphology and decreased quantity, respiration, permeability, and membrane potential, along with significantly increased mitophagy-related protein ATG5 and LC3II/LC3 levels and decreased p62 levels. Expression of hypoxia-associated autophagy genes Becn1, Hif1, Bnip3, Bnip3l, and Fundc1 was significantly higher in the IH-8w group. Significantly increased LAMP2, CTSB, and ACP2 levels in IH-8w cells further indicated impaired lysosomal function. Lysophagy-related protein LAMP1, LC3II/LC3I, and TFEB levels were significantly increased in the IH-8w group, whereas p62 level was significantly decreased. The above listed evidence indicated damage to the mitochondria and lysosomes, as well as stimulation of mitophagy and lysophagy in IH-treatment OSAHS rat model. After withdrawing IH and culturing for 4 weeks in normal conditions, the cognitive function of rats improved, and mitophagy and lysophagy decreased. Our findings indicate that IH impairs cognitive function and promotes mitophagy and lysophagy in an OSAHS rat model, and IH withdrawal recovered the above effects.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Tian, Yan Zhang, Wei Li, GenTan Xie, JunJing Wu, Jing Liu
{"title":"Astragaloside IV Inhibits Lung Injury and Fibrosis Induced by PM2.5 by Targeting RUNX1 Through miR-362-3p.","authors":"Hao Tian, Yan Zhang, Wei Li, GenTan Xie, JunJing Wu, Jing Liu","doi":"10.1007/s12033-024-01320-5","DOIUrl":"https://doi.org/10.1007/s12033-024-01320-5","url":null,"abstract":"<p><p>To discover the molecular mechanism of Astragaloside IV (AS IV) in PM2.5-induced lung injury and pulmonary fibrosis (PF). A lung injury rat model was induced by PM2.5 and injected intraperitoneally with AS IV. Lungs were harvested to evaluate lung tissue injury and apoptosis. Rat alveolar epithelial cells L2 were exposed to PM2.5 and treated with AS IV. After cellular transfection, cell proliferation, LDH production, and apoptosis were measured. In both models, inflammatory factors and fibrotic indices were measured by ELISA and Western blot. miR-362-3p and RUNX1 interplay was explored and confirmed. Administration of AS IV attenuated PM2.5-induced lung tissue injury, inflammation, apoptosis, and PF in rats. AS IV enhanced proliferation and reduced LDH release, apoptosis, inflammation, and PF in PM2.5-treated L2 cells. MiR-362-3p upregulation improved PM2.5-induced L2 cell injury. AS IV improved PM2.5-induced lung injury by upregulating miR-362-3p. miR-362-3p had an inhibition effect on RUNX1 expression. RUNX1 upregulation weakened the therapeutic effect of AS IV on PM2.5-induced alveolar epithelial cell injury. AS IV inhibits lung injury and PF induced by PM2.5 by targeting RUNX1 through upregulation of miR-362-3p.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Qiang Jin Mixture Promotes Osteogenic Differentiation of MC3T3-E1 Cells via BMP2/Smads Pathway and its Network Pharmacology Study.","authors":"Weiyue Gong, Yao Zhu, Limin Wang","doi":"10.1007/s12033-024-01313-4","DOIUrl":"https://doi.org/10.1007/s12033-024-01313-4","url":null,"abstract":"<p><p>The study aimed to explore the potential of QiangJin mixture (QJM), a Chinese herbal compound prescription, in regulating MC3T3-E1 cell differentiation and to analyze the ingredients and therapeutic targets of QJM against osteoporosis based on network pharmacology. MC3T3-E1 cells were incubated with different concentrations of QJM-contained rat serum (5, 10, or 20%). After 14 days of cell culture, Alizarin Red staining was performed to assess the mineralization ability of osteoblasts. RT-qPCR was used to measure mRNA levels of osteogenesis-related genes. Western blot was conducted to measure protein levels of factors related to the BMP2/Smads pathway. Functional and pathway enrichment of overlapping targets for QJM and osteoporosis were analyzed using gene ontology and KEGG analyses. As shown by experimental results, QJM-contained serum led to calcium deposition, increased expression levels of osteogenesis-related genes, and activated BMP2/Smad/Runx2 signaling in MC3T3-E1 cells. A total of 125 active compounds and 162 disease-related targets were identified. The core targets were MAPK8, TP53, ESR1, STAT3, MAPK3, IL6, NFKB1, JUN, MAPK1 and AKT1. In conclusion, QJM promotes the osteogenic differentiation of MC3T3-E1 cells by activating the BMP2/Smads signaling. Additionally, QJM is an anti-osteoporotic mixture by regulating diverse therapeutic targets and signaling pathways.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abel Onolunosen Abhadionmhen, Caroline Ngozi Asogwa, Modesta Ero Ezema, Royransom Chiemela Nzeh, Nnamdi Johnson Ezeora, Stanley Ebhohimhen Abhadiomhen, Stephenson Chukwukanedu Echezona, Collins Nnalue Udanor
{"title":"Machine Learning Approaches for Microorganism Identification, Virulence Assessment, and Antimicrobial Susceptibility Evaluation Using DNA Sequencing Methods: A Systematic Review.","authors":"Abel Onolunosen Abhadionmhen, Caroline Ngozi Asogwa, Modesta Ero Ezema, Royransom Chiemela Nzeh, Nnamdi Johnson Ezeora, Stanley Ebhohimhen Abhadiomhen, Stephenson Chukwukanedu Echezona, Collins Nnalue Udanor","doi":"10.1007/s12033-024-01309-0","DOIUrl":"https://doi.org/10.1007/s12033-024-01309-0","url":null,"abstract":"<p><p>Microbial infections pose a substantial global health challenge, particularly impacting immunocompromised individuals and exacerbating the issue of antimicrobial resistance (AMR). High virulence of pathogens can lead to severe infections and prolonged antimicrobial treatment, increasing the risk of developing resistant strains. Integrating machine-learning (ML) with DNA sequencing technologies offers potential solutions by enhancing microbial identification, virulence assessment, and antimicrobial susceptibility evaluation. This review explores recent advancements in these integrated approaches, addressing current limitations and identifying gaps in the literature. A comprehensive literature search was conducted across databases including PubMed, Scopus, Web of Science, and IEEE Xplore, covering publications from January 2014 to June 2024. Using a detailed Boolean search string, relevant studies focusing on ML applications in microorganism identification, antimicrobial susceptibility testing, and microbial virulence were included. The screening process involved a two-stage review of titles, abstracts, and full texts, with data extraction and critical appraisal performed using the QIAO tool. Data were analyzed through narrative synthesis to identify common themes and innovations. Out of 1,650 initially identified records, 19 studies met the inclusion criteria. These studies primarily focused on AMR, with additional research on microbial virulence and identification. Machine learning algorithms such as Random Forest, Support Vector Machines, and Convolutional Neural Networks, combined with DNA sequencing techniques like Whole Genome Sequencing and Metagenomic Sequencing, demonstrated significant advancements in predictive accuracy and efficiency. High-quality studies achieved impressive performance metrics, including F1-scores up to 0.88 and AUC scores up to 0.96. The integration of ML and DNA sequencing technologies has significantly enhanced microbial analysis, improving the identification of pathogens, assessment of virulence, and evaluation of antimicrobial susceptibility. Despite advancements, challenges such as data quality, high costs, and model interpretability persist. This review highlights the need for continued innovation and provides recommendations for future research to address these limitations and improve disease management and public health strategies. The systematic review is registered with PROSPERO (CRD42024571347).</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bimal K Chetri, S S Sonu, Rahul G Shelke, Sudip Mitra, Latha Rangan
{"title":"De Novo Sequencing of Drymaria villosa and Comparative Analysis of Plastome in Caryophyllaceae Across 23 Species.","authors":"Bimal K Chetri, S S Sonu, Rahul G Shelke, Sudip Mitra, Latha Rangan","doi":"10.1007/s12033-024-01317-0","DOIUrl":"https://doi.org/10.1007/s12033-024-01317-0","url":null,"abstract":"<p><p>Plant plastome are well studied due to their essential roles in photosynthesis and plant development. Comparative studies among plastome of closely related genera or families are limited, hindering our understanding of evolutionary changes and adaptation. This study presents a comparative analysis of 23 Caryophyllaceae plastome revealing a dynamic interplay of conserved and variable features. The genome size exhibited a moderate coefficient of variation (CV) of 2.58%. The large single-copy (LSC) and small single-copy (SSC) regions were highly conserved, with CVs of 2.55% and 2.00%, respectively. In contrast, the inverted repeat (IR) regions displayed greater variability, with a CV of 4.23%, indicating dynamic evolutionary processes. Exon counts varied significantly (CV 17.20%), while intron counts showed some variability (CV 7.79%), reflecting diverse gene structures. Coding sequences had moderate variability (CV 3.67%), while non-coding sequences varied more (CV 5.05%). tRNA counts were slightly variable (CV 2.67%), and GC content was notably consistent (CV 0.40%). This study includes the newly sequenced plastome of Drymaria villosa (GenBank accession OR790517), confirming its placement within Caryophyllaceae with significant diversification through phylogenetic analysis. Correlations (> 0.6) among plastome components and genome size reflect their tight evolutionary linkage, enhancing our understanding of plastome evolution in Caryophyllaceae and aiding future investigations into the ecological and medicinal potential of D. villosa and related species.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hsa_circ_0109320 Serves as a Novel Circular RNA Biomarker in Non-small Cell Lung Cancer by Promoting Metastasis.","authors":"Xiaoyan Guo, Hongyan Yu, Xiansheng Wang, Shifeng Zhao, Chunyan Wang, Shuai Wang","doi":"10.1007/s12033-024-01306-3","DOIUrl":"https://doi.org/10.1007/s12033-024-01306-3","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC), including squamous cell carcinoma and adenocarcinoma, ranks among the top 10 cancers worldwide in terms of prevalence and mortality. NSCLC, a highly malignant tumor, exhibits distant invasion and migration as well as an unfavorable prognosis. As an innovative circular RNA, hsa _circ_0109320 (circ_0109320) has been recognized as a promising cancer modulator. However, our understanding of the influence of circ_0109320 in NSCLC remains insufficient. Our research explored the clinical significance and effects of circ_0109320 on oncogenic non-small cell lung cancer (NSCLC) phenotypes. Microarray analysis and qPCR indicated that circ_0109320 expression in NSCLC specimens increased relative to that in adjacent normal tissues and was further elevated in metastatic lymph nodes. The specimens acquired from 25 patients confirmed these findings. Additionally, circ_0109320 indicated a good score (AUC = 0.688, P = 0.013) on the ROC curves, which suggests its suitability as a promising biomarker for lung cancer. Meanwhile, circ_0109320 was noticeably upregulated in lung cancer (LC) cell lines compared to human bronchial epithelial cells. Next, we performed loss- and gain-of-function experiments to examine the role of circ_0109320 in the tumor phenotypes of the cell lines. We observed that depletion or overexpression of circ_0109320 did not alter cell viability. However, the ectopic removal of circ_0109320 repressed the migration and invasion of A549 and SK-MES-1 cells, whereas circ_0109320 overexpression promoted cell migration and invasion. Furthermore, the examination of epithelial-mesenchymal transition (EMT) markers indicated that circ_0109320 elevates cell EMT activity. In conclusion, circ_0109320 level was highly associated with increased tumor cell proliferation and metastasis. circ_0109320 could be a promising predictor of clinical outcomes and a reliable target to treat NSCLC by inhibiting metastasis.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Surya Venkatesh, P Mohammed Manaz, M Harish Priya, G Ambiga, Soumyo Basu
{"title":"Shedding Light on the Molecular Diversities of miRNA in Cancer- an Exquisite Mini Review.","authors":"Surya Venkatesh, P Mohammed Manaz, M Harish Priya, G Ambiga, Soumyo Basu","doi":"10.1007/s12033-024-01312-5","DOIUrl":"https://doi.org/10.1007/s12033-024-01312-5","url":null,"abstract":"<p><p>Short non-coding ribonucleic acids are also known as \"Micro ribonucleic acids (miRNAs)\". The miRNAs make a contribution to the regulation of genes and mitigation of cancer cell growth in humans. miRNAs play a significant role in several BPs, namely apoptosis, cell cycle progression, and development. It is well-recognized that miRNAs are crucial for the tumors' growth and also serve as Tumor Suppressors (TSs) or oncogenes. As miRNAs also act as an effective tumor suppressor, studying the molecular diversities of the miRNAs makes way to minimize cancer progression and the corresponding death rates in the future. Therefore, miRNAs along with their Biological Processes (BPs) and molecular diversities are thoroughly researched in this paper. Consequently, miRNAs particularly target their 3' UnTranslated Region (3'-UTR) for controlling the target mRNAs' stability and protein translation. So, this study also expresses the impact of microRNA variants in various cancer cells, namely Breast cancer, Gastric or stomach cancer, ovarian cancer, and lymphocytic leukemia. Furthermore, the database named PhenomiR and commercial kits that are used in the miRNA data analysis are discussed in this article to provide extensive knowledge about the molecular diversity analysis of miRNA and their influences on cancerous cells.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2024-11-01Epub Date: 2023-11-02DOI: 10.1007/s12033-023-00920-x
Elham Rastkhah, Faezeh Fatemi, Parvaneh Maghami
{"title":"Optimizing the Metal Bioreduction Process in Recombinant Shewanella azerbaijanica Bacteria: A Novel Approach via mtrC Gene Cloning and Nitrate-Reducing Pathway Destruction.","authors":"Elham Rastkhah, Faezeh Fatemi, Parvaneh Maghami","doi":"10.1007/s12033-023-00920-x","DOIUrl":"10.1007/s12033-023-00920-x","url":null,"abstract":"<p><p>Environmental pollution is growing every day in terms of the increase in population, industrialization, and urbanization. Shewanella azerbaijanica is introduced as a highly potent bacterium in metal bioremediation. The mtrC gene was selected as a cloning target to improve electron flux chains in the EET (extracellular electron transfer) pathway. Using the SDM (site-directed mutagenesis) technique, the unique gene assembly featured the mtrC gene sandwiched between two napD/B genes to disrupt the nitrate reduction pathway, which serves as the primary metal reduction competitor. Shew-mtrC gene construction was transferred to expression plasmid pET28a (+) in the expression host bacteria (E. coli BL21 and S. azerbaijanica), in pUC57, cloning plasmid, which was transferred to the cloning host bacteria E. coli Top10 and S. azerbaijanica. All cloning procedures (i.e., synthesis, insertion, transformation, cloning, and protein expression) were verified and confirmed by precise tests. ATR-FTIR analysis, CD, western blotting, affinity chromatography, SDS-PAGE, and other techniques were used to confirm the expression and structure of the MtrC protein. The genome sequence and primers were designed according to the submitted Shewanella oneidensis MR-1 genome, the most similar bacteria to this native species. The performance of recombinant S. azerbaijanica bacterium in metal bioremediation, as sustainable strategy, has to be verified by more research.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3150-3163"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}