Journal of Biomedical Science最新文献

{"title":"The Data Artifacts Glossary: a community-based repository for bias on health datasets.","authors":"Rodrigo R Gameiro, Naira Link Woite, Christopher M Sauer, Sicheng Hao, Chrystinne Oliveira Fernandes, Anna E Premo, Alice Rangel Teixeira, Isabelle Resli, An-Kwok Ian Wong, Leo Anthony Celi","doi":"10.1186/s12929-024-01106-6","DOIUrl":"10.1186/s12929-024-01106-6","url":null,"abstract":"<p><strong>Background: </strong>The deployment of Artificial Intelligence (AI) in healthcare has the potential to transform patient care through improved diagnostics, personalized treatment plans, and more efficient resource management. However, the effectiveness and fairness of AI are critically dependent on the data it learns from. Biased datasets can lead to AI outputs that perpetuate disparities, particularly affecting social minorities and marginalized groups.</p><p><strong>Objective: </strong>This paper introduces the \"Data Artifacts Glossary\", a dynamic, open-source framework designed to systematically document and update potential biases in healthcare datasets. The aim is to provide a comprehensive tool that enhances the transparency and accuracy of AI applications in healthcare and contributes to understanding and addressing health inequities.</p><p><strong>Methods: </strong>Utilizing a methodology inspired by the Delphi method, a diverse team of experts conducted iterative rounds of discussions and literature reviews. The team synthesized insights to develop a comprehensive list of bias categories and designed the glossary's structure. The Data Artifacts Glossary was piloted using the MIMIC-IV dataset to validate its utility and structure.</p><p><strong>Results: </strong>The Data Artifacts Glossary adopts a collaborative approach modeled on successful open-source projects like Linux and Python. Hosted on GitHub, it utilizes robust version control and collaborative features, allowing stakeholders from diverse backgrounds to contribute. Through a rigorous peer review process managed by community members, the glossary ensures the continual refinement and accuracy of its contents. The implementation of the Data Artifacts Glossary with the MIMIC-IV dataset illustrates its utility. It categorizes biases, and facilitates their identification and understanding.</p><p><strong>Conclusion: </strong>The Data Artifacts Glossary serves as a vital resource for enhancing the integrity of AI applications in healthcare by providing a mechanism to recognize and mitigate dataset biases before they impact AI outputs. It not only aids in avoiding bias in model development but also contributes to understanding and addressing the root causes of health disparities.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"14"},"PeriodicalIF":9.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilisation of an in vivo malaria model to provide functional proof for RhopH1/CLAG essentiality and conserved orthology with P. falciparum.","authors":"Mitchell L Trickey, Mrittika Chowdury, Georgina Bramwell, Natalie A Counihan, Tania F de Koning-Ward","doi":"10.1186/s12929-024-01105-7","DOIUrl":"10.1186/s12929-024-01105-7","url":null,"abstract":"<p><strong>Background: </strong>Malaria parasites establish new permeation pathways (NPPs) at the red blood cell membrane to facilitate the transport of essential nutrients from the blood plasma into the infected host cell. The NPPs are critical to parasite survival and, therefore, in the pursuit of novel therapeutics are an attractive drug target. The NPPs of the human parasite, P. falciparum, have been linked to the RhopH complex, with the monoallelic paralogues clag3.1 and clag3.2 encoding the protein RhopH1/CLAG3 that likely forms the NPP channel-forming component. Yet curiously, the combined knockout of both clag3 genes does not completely eliminate NPP function. The essentiality of the clag3 genes is, however, complicated by three additional clag paralogs (clag2, clag8 and clag9) in P. falciparum that could also be contributing to NPP formation.</p><p><strong>Methods: </strong>Here, the rodent malaria species, P. berghei, was utilised to investigate clag essentiality since it contains only two clag genes, clagX and clag9. Allelic replacement of the regions encompassing the functional components of P. berghei clagX with either P. berghei clag9 or P. falciparum clag3.1 examined the relationship between the two P. berghei clag genes as well as functional orthology across the two species. An inducible P. berghei clagX knockout was created to examine the essentiality of the clag3 ortholog to both survival and NPP functionality.</p><p><strong>Results: </strong>It was revealed P. berghei CLAGX and CLAG9, which belong to two distinct phylogenetic clades, have separate non-complementary functions, and that clagX is the functional orthologue of P. falciparum clag3. The inducible clagX knockout in conjunction with a guanidinium chloride induced-haemolysis assay to assess NPP function provided the first evidence of CLAG essentiality to Plasmodium survival and NPP function in an in vivo model of infection.</p><p><strong>Conclusions: </strong>This work provides valuable insight regarding the essentiality of the RhopH1 clag genes to the NPPs functionality and validates the continued investigation of the RhopH complex as a therapeutic target to treat malaria infections.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"13"},"PeriodicalIF":9.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in mice.","authors":"Elle Em Scheijen, Naomi Veeningen, Sam Duwé, Anna Ivanova, Jana Van Broeckhoven, Sven Hendrix, David M Wilson","doi":"10.1186/s12929-024-01104-8","DOIUrl":"10.1186/s12929-024-01104-8","url":null,"abstract":"<p><strong>Background: </strong>Deficient DNA repair and excessive DNA damage contribute to neurodegenerative disease. However, the role of DNA damage and repair in spinal cord injury (SCI) is unclear. SCI, a debilitating disruption of the structural and biological network of the spinal cord, is characterized by oxidative stress. Nevertheless, the pathophysiological mechanisms leading to neuronal loss following SCI remain incompletely defined.</p><p><strong>Methods: </strong>Using a contusion model, a severe SCI was induced at the L1 spinal level in C57Bl/6J mice. The temporal and spatial presence of DNA damage was then determined via immunolabeling for the DNA damage marker, γH2AX, from 1 h post-injury (hpi) to 28 days post-injury (dpi).</p><p><strong>Results: </strong>Our analysis revealed that increased DNA damage foci were present from 1 hpi to 3 dpi in SCI mice relative to controls (sham surgery and naive), with the damage signal spreading over time longitudinally from the affected area to more rostral and caudal regions. Co-labeling of γH2AX with NeuN revealed neuronal specificity of DNA damage, with increased early cell death (pan-nuclear γH2AX) peaking at 1 dpi and apoptosis (cleaved Caspase-3) arising later at 3 dpi.</p><p><strong>Conclusion: </strong>Our study indicates a possible role of DNA damage in neuronal loss following SCI and highlights the need for early interventions targeting DNA repair to preserve neuronal tissue.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"12"},"PeriodicalIF":9.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The endoplasmic reticulum degradation-enhancing α-mannosidase-like protein 3 attenuates the unfolded protein response and has pro-survival and pro-viral roles in hepatoma cells and hepatocellular carcinoma patients.","authors":"Alina-Veronica Ghionescu, Mihaela Uta, Andrei Sorop, Catalin Lazar, Petruta R Flintoaca-Alexandru, Gabriela Chiritoiu, Livia Sima, Stefana-Maria Petrescu, Simona Olimpia Dima, Norica Branza-Nichita","doi":"10.1186/s12929-024-01103-9","DOIUrl":"10.1186/s12929-024-01103-9","url":null,"abstract":"<p><strong>Background: </strong>Chronic hepatitis B virus (HBV) infection is a major risk for development of hepatocellular carcinoma (HCC), a frequent malignancy with a poor survival rate. HBV infection results in significant endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) signaling, a contributing factor to carcinogenesis. As part of the UPR, the ER-associated degradation (ERAD) pathway is responsible for removing the burden of misfolded secretory proteins, to re-establish cellular homeostasis. Emerging evidence indicates consistent upregulation of ERAD factors, including members of the ER degradation-enhancing alpha-mannosidase-like protein (EDEM) family in infection and various tumor types. However, the significance of this gene expression pattern in HBV-driven pathology is just beginning to be deciphered.</p><p><strong>Methods: </strong>In this study we quantified the expression of the ERAD factor EDEM3, in a cohort of HCC patients with and without HBV infection, and validated our results by analysis of publically available transcriptomic and microarray data sets. We performed mechanistic studies in HepaRG cells with modulated EDEM3 expression to address UPR, ERAD, autophagy and apoptosis signaling, and their consequences on HBV infection.</p><p><strong>Results: </strong>Our work revealed significantly elevated EDEM3 expression in HCC tissues irrespective of HBV infection, while the highest levels were observed in tissues from HBV-infected patients. Investigation of published transcriptomic data sets confirmed EDEM3 upregulation in independent HCC patient cohorts, associated with tumor progression, poor survival prognosis and resistance to therapy. EDEM3-overexpressing hepatic cells exhibited attenuated UPR and activated secretory autophagy, which promoted HBV production. Conversely, cell depletion of EDEM3 resulted in significant ER stress inducing pro-apoptotic mechanisms and cell death.</p><p><strong>Conclusions: </strong>We provide evidence of major implications of the ERAD pathway in HBV infection and HCC development and progression. Our results suggest that ERAD activation in HBV-infected cells is a protective mechanism against prolonged ER stress, potentially contributing to establishment of chronic HBV infection and promoting tumorigenesis. Developing specific inhibitors for ERAD factors may be an attractive approach to improve efficiency of current antiviral and anticancer therapies.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"11"},"PeriodicalIF":9.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in nucleic acid-based cancer vaccines.","authors":"Hung-Chun Liao, Shih-Jen Liu","doi":"10.1186/s12929-024-01102-w","DOIUrl":"10.1186/s12929-024-01102-w","url":null,"abstract":"<p><p>Nucleic acid vaccines have emerged as crucial advancements in vaccine technology, particularly highlighted by the global response to the COVID-19 pandemic. The widespread administration of mRNA vaccines against COVID-19 to billions globally marks a significant milestone. Furthermore, the approval of an mRNA vaccine for Respiratory Syncytial Virus (RSV) this year underscores the versatility of this technology. In oncology, the combination of mRNA vaccine encoding neoantigens and immune checkpoint inhibitors (ICIs) has shown remarkable efficacy in eliciting protective responses against diseases like melanoma and pancreatic cancer. Although the use of a COVID-19 DNA vaccine has been limited to India, the inherent stability at room temperature and cost-effectiveness of DNA vaccines present a viable option that could benefit developing countries. These advantages may help DNA vaccines address some of the challenges associated with mRNA vaccines. Currently, several trials are exploring the use of DNA-encoded neoantigens in combination with ICIs across various cancer types. These studies highlight the promising role of nucleic acid-based vaccines as the next generation of immunotherapeutic agents in cancer treatment. This review will delve into the recent advancements and current developmental status of both mRNA and DNA-based cancer vaccines.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"10"},"PeriodicalIF":9.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting enolase 1 reverses bortezomib resistance in multiple myeloma through YWHAZ/Parkin axis.","authors":"Xuejie Gao, Qilin Feng, Qikai Zhang, Yifei Zhang, Chaolu Hu, Li Zhang, Hui Zhang, Guanli Wang, Ke Hu, Mengmeng Ma, Zhuning Wang, Yujie Liu, Dong An, Hongfei Yi, Yu Peng, Xiaosong Wu, Gege Chen, Xinyan Jia, Haiyan Cai, Jumei Shi","doi":"10.1186/s12929-024-01101-x","DOIUrl":"10.1186/s12929-024-01101-x","url":null,"abstract":"<p><strong>Background: </strong>Enolase 1 (ENO1) is a conserved glycolytic enzyme that regulates glycolysis metabolism. However, its role beyond glycolysis in the pathophysiology of multiple myeloma (MM) remains largely elusive. Herein, this study aimed to elucidate the function of ENO1 in MM, particularly its impact on mitophagy under bortezomib-induced apoptosis.</p><p><strong>Methods: </strong>The bone marrow of clinical MM patients and healthy normal donors was used to compare the expression level of ENO1. Using online databases, we conducted an analysis to examine the correlation between ENO1 expression and both clinicopathological characteristics and patient outcomes. To investigate the biological functions of ENO1 in MM and the underlying molecular mechanisms involved, we conducted the following experiment: construction of a subcutaneous graft tumor model, co-immunoprecipitation, western blot, quantitative real-time polymerase chain reaction, immunohistochemistry, flow cytometry, and cell functional assays.</p><p><strong>Results: </strong>ENO1 was identified as an unfavorable prognostic factor in MM. ENO1 knockdown suppresses tumorigenicity and causes cell cycle arrest. Inhibition of ENO1-regulated mitophagy sensitizes tumor cells to apoptosis. ENO1 enhanced the stability of the YWHAZ protein by increasing the acetylation of lysine in YWHAZ while antagonizing its ubiquitination, which in turn promoted mitophagy. HDAC6 mediates the deacetylation of YWHAZ by deacetylating the K138 site of YWHAZ. Inhibition of HDAC6 increased YWHAZ acetylation and decreased YWHAZ ubiquitination. Furthermore, combination treatment with bortezomib and pharmaceutical agents targeting ENO1 has synergistic anti-MM effects both in vivo and in vitro.</p><p><strong>Conclusion: </strong>Our data suggest that ENO1 promotes MM tumorigenesis and progression. ENO1 activates mitophagy by promoting the stability of YWHAZ and inhibits apoptosis and thus, leads to the drug resistance. ENO1-dependent mitophagy promotes MM proliferation and suppresses the level of bortezomib-induced apoptosis. Inhibition of ENO1 may represent a potential strategy to reverse the resistance of MM to bortezomib.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"9"},"PeriodicalIF":9.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenosine RNA modification regulates the transcription of SLC7A11 through KDM6B and GATA3 to modulate ferroptosis.","authors":"Haisheng Zhang, Cheng Yi, Jianing Li, Yunqing Lu, Haoran Wang, Lijun Tao, Jiawang Zhou, Yonghuang Tan, Jiexin Li, Zhuojia Chen, Gholamreza Asadikaram, Jie Cao, Jianxin Peng, Wanglin Li, Junming He, Hongsheng Wang","doi":"10.1186/s12929-024-01100-y","DOIUrl":"10.1186/s12929-024-01100-y","url":null,"abstract":"<p><strong>Background: </strong>Recent studies indicate that N6-methyladenosine (m⁶A) RNA modification may regulate ferroptosis in cancer cells, while its molecular mechanisms require further investigation.</p><p><strong>Methods: </strong>Liquid Chromatography-Tandem Mass Spectrometry (HPLC/MS/MS) was used to detect changes in m⁶A levels in cells. Transmission electron microscopy and flow cytometry were used to detect mitochondrial reactive oxygen species (ROS). RNA sequencing (RNA-seq) was employed to analyze the factors regulating ferroptosis. Chromatin immunoprecipitation (ChIP) was used to assess the binding of regulatory factors to the SLC7A11 promoter, and a Dual-Luciferase reporter assay measured promoter activity of SLC7A11. The dm⁶ACRISPR system was utilized for the demethylation of specific transcripts. The Cancer Genome Atlas Program (TCGA) database and immunohistochemistry validated the role of the METTL3/SLC7A11 axis in cancer progression.</p><p><strong>Results: </strong>The m⁶A methyltransferase METTL3 was upregulated during cancer cell ferroptosis and facilitated erastin-induced ferroptosis by enhancing mitochondrial ROS. Mechanistic studies showed that METTL3 negatively regulated the transcription and promoter activity of SLC7A11. Specifically, METTL3 induced H3K27 trimethylation of the SLC7A11 promoter by suppressing the mRNA stability of H3K27 demethylases KDM6B. Furthermore, METTL3 suppressed the expression of GATA3, which regulated SLC7A11 transcription by binding to the putative site at - 597 to - 590 of the SLC7A11 promoter. METTL3 decreased the precursor mRNA stability of GATA3 through m⁶A/YTHDF2-dependent recruitment of the 3'-5' exoribonuclease Dis3L2. Targeted demethylation of KDM6B and GATA3 m⁶A using the dm⁶ACRISPR system significantly increased the expression of SLC7A11. Moreover, the transcription factor YY1 was responsible for erastin-induced upregulation of METTL3 by binding to its promoter-proximal site. In vivo and clinical data supported the positive roles of the METTL3/SLC7A11 axis in tumor growth and progression.</p><p><strong>Conclusions: </strong>METTL3 regulated the transcription of SLC7A11 through GATA3 and KDM6B to modulate ferroptosis in an m⁶A-dependent manner. This study provides a novel potential strategy and experimental support for the future treatment of cancer.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"8"},"PeriodicalIF":9.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.","authors":"Zhipeng Cao, Sadia Quazi, Sakshi Arora, Laura D Osellame, Ingrid J Burvenich, Peter W Janes, Andrew M Scott","doi":"10.1186/s12929-024-01099-2","DOIUrl":"10.1186/s12929-024-01099-2","url":null,"abstract":"<p><p>Research into cancer treatment has been mainly focused on developing therapies to directly target cancer cells. Over the past decade, extensive studies have revealed critical roles of the tumour microenvironment (TME) in cancer initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) have emerged as one of the primary contributors in shaping TME, creating a favourable environment for cancer development. Many preclinical studies have identified promising targets on CAFs, demonstrating remarkable efficacy of some CAF-targeted treatments in preclinical models. Encouraged by these compelling findings, therapeutic strategies have now advanced into clinical evaluation. We aim to provide a comprehensive review of relevant subjects on CAFs, including CAF-related markers and targets, their multifaceted roles, and current landscape of ongoing clinical trials. This knowledge can guide future research on CAFs and advocate for clinical investigations targeting CAFs.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"7"},"PeriodicalIF":9.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11715488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel human specific lncRNA MEK6-AS1 regulates adipogenesis and fatty acid biosynthesis by stabilizing MEK6 mRNA.","authors":"Di Li, Yunhua Chen, Xingyu Zhu, Yanlei Yang, Hongling Li, Robert Chunhua Zhao","doi":"10.1186/s12929-024-01098-3","DOIUrl":"https://doi.org/10.1186/s12929-024-01098-3","url":null,"abstract":"<p><strong>Background: </strong>Obesity is becoming one of the major non-communicable diseases with increasing incidence and risks that cannot be ignored. However effective and safe clinical treatment strategies still need to be deeply explored. Increased number and volume of adipocytes lead to overweight and obesity. The aim of our work is to identify lncRNAs that have important regulatory in differentiation of human mesenchymal stem cells (MSCs) into adipocytes, and to provide effective targets for clinical prevention and treatment of obesity and related metabolic disorders.</p><p><strong>Methods: </strong>We extracted primary MSCs from human adipose tissue, and conducted expression profile analysis of lncRNAs during adipogenic differentiation of MSCs to screen changed lncRNAs. Characteristics of lncRNA were revealed mainly by RACE and RNA FISH. Loss- and gain-of function experiments in vivo and in vitro were used to analyze effects of lncRNA. Targeted metabolomics was utilized to detect levels of free fatty acids. RNA pull-down, mRNA stability tests, etc. were employed to explore mechanisms of lncRNA.</p><p><strong>Results: </strong>Human-specific lncRNA, we named it MEK6-AS1, was the most up-regulated transcript during adipogenic differentiation of MSCs. MEK6-AS1 was highly expressed in adipose tissue samples from individuals with BMI ≥ 25 and positively correlated with adipogenic marker genes in these samples. Knocking down lncRNA inhibited expression of adipogenic differentiation markers and ectopic adipogenesis, reducing contents of various free fatty acids, as well as promoting osteogenic differentiation. Overexpression of lncRNA had the opposite effects to the above processes. We also found that MEK6-AS1 was elevated during hepatic steatosis organoid generation. Mechanistically, MEK6-AS1 worked partially through stabilization of MEK6 mRNA by NAT10.</p><p><strong>Conclusions: </strong>We have identified a human-specific lncRNA (MEK6-AS1) with position information in the genomic database but has not been extensively reported. We demonstrated that MEK6-AS1 as a novel lncRNA involved in adipogenic differentiation and adipogenesis, fatty acid metabolism, and osteogenic differentiation. We found that MEK6-AS1 may exert its effect by enhancing MEK6 mRNA stability through NAT10. Our study may provide insights into implication of lncRNAs in stem cell biology and offer a new potential therapeutic target for the prevention and treatment of obesity and other related disease.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"6"},"PeriodicalIF":9.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition.","authors":"Yulong Yu, Han Yin, Bili Wu, Weiheng Zhao, Yuan Wang, Aifeina Aili, Mu Yang, Qianqian Yu, Xianglin Yuan","doi":"10.1186/s12929-024-01097-4","DOIUrl":"https://doi.org/10.1186/s12929-024-01097-4","url":null,"abstract":"<p><strong>Background: </strong>The association between the intestinal microbiota and colorectal cancer (CRC) has been extensively studied, with Fusobacterium nucleatum (F. nucleatum, FN) being found in high abundance in colorectal cancer tissues. Previous research has emphasized the significant role of F. nucleatum in the occurrence of CRC. However, the impact of F. nucleatum on CRC liver metastasis has not been well understood.</p><p><strong>Methods: </strong>The effects of F. nucleatum on metastasis ability of CRC cell were evaluated in vitro were examined by wound-healing assay and transwell assay. The mouse model of CRC liver metastasis was constructed by spleen injection, and the degree of liver metastasis was assessed by in vivo bioluminescence imaging. The gene expression changes in CRC cells after co-culture with F. nucleatum was analyzed through transcriptome sequencing. qRT-PCR and Western Blot assays were performed to validate the expression of related genes and proteins.</p><p><strong>Results: </strong>The metastasis ability of CRC cells was significantly enhanced after co-culture with F. nucleatum in vitro. In the mouse model, F. nucleatum also promoted the development of liver metastasis in CRC. Mechanistically, F. nucleatum infection increased the expression of IL-8 by downregulated the level of miR-5692a, a regulatory microRNA of IL-8. This led to the activation of the ERK pathway and resulted in the epithelial-mesenchymal transition (EMT) of CRC cells.</p><p><strong>Conclusions: </strong>Our results suggest that F. nucleatum promotes CRC liver metastasis by inducing epithelial-mesenchymal transition through the miR-5692a/IL-8 axis. These findings provide new insights for the prevention and treatment of colorectal cancer liver metastasis.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"5"},"PeriodicalIF":9.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}