Advanced biologyPub Date : 2024-12-01Epub Date: 2024-11-05DOI: 10.1002/adbi.202400323
Wan Liang, Yuke Ren, Yusu Wang, Weijian Chen, Ziyao Mo, Chenglu Yang, Ke Nie
{"title":"Xiao-Ban-Xia Decoction Alleviates Chemotherapy-Induced Nausea and Vomiting by Inhibiting Ferroptosis via Activation of The Nrf2/SLC7A11/GPX4 Pathway.","authors":"Wan Liang, Yuke Ren, Yusu Wang, Weijian Chen, Ziyao Mo, Chenglu Yang, Ke Nie","doi":"10.1002/adbi.202400323","DOIUrl":"10.1002/adbi.202400323","url":null,"abstract":"<p><p>Chemotherapy-induced nausea and vomiting (CINV) represents the common gastrointestinal side effect for cancer patients. Xiao-Ban-Xia decoction (XBXD), a classical anti-emetic traditional Chinese medicine formula, is frequently used for the clinical treatment of CINV. This study used a cisplatin-induced rat pica model to explore whether the anti-emetic mechanism of XBXD in treating CINV is related to ferroptosis. The inflammatory damage of the gastrointestinal tract is evaluated by HE staining and ELISA. The degree of ferroptosis are validated by the iron deposition, the levels of ROS, MDA, and GSH, and the ultrastructure of mitochondria in the gastric antrum and ileum. The potential ferroptosis-related targets of XBXD against CINV are screened by network pharmacology and further assessed by Western blot. XBXD significantly decreased the kaolin consumption in rats, and improved the inflammatory pathological damage, with decreased levels of HMGB1, IL-1β, and TNF-α. Furthermore, XBXD significantly suppressed ferroptosis, as indicated by the improvement of iron deposition, mitochondrial abnormalities, and oxidative stress. The network pharmacology and Western blot results indicated that XBXD activated the Nrf2/SLC7A11/GPX4 signaling pathway. This study proved that XBXD activates the Nrf2/SLC7A11/GPX4 signaling pathway, thereby inhibiting ferroptosis, which represents a critical anti-emetic mechanism of XBXD in combatting CINV.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400323"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581928","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}
Advanced biologyPub Date : 2024-12-01Epub Date: 2024-10-23DOI: 10.1002/adbi.202400265
Yung-Yi Chen, Jack Sullivan, Shaun Hanley, Joshua Price, Mohammad A Tariq, Luke C McIlvenna, Martin Whitham, Archana Sharma-Oates, Paul Harrison, Janet M Lord, Jon Hazeldine
{"title":"Impact of Senescent Cell-Derived Extracellular Vesicles on Innate Immune Cell Function.","authors":"Yung-Yi Chen, Jack Sullivan, Shaun Hanley, Joshua Price, Mohammad A Tariq, Luke C McIlvenna, Martin Whitham, Archana Sharma-Oates, Paul Harrison, Janet M Lord, Jon Hazeldine","doi":"10.1002/adbi.202400265","DOIUrl":"10.1002/adbi.202400265","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are components of the senescence-associated secretory phenotype (SASP) that influence cellular functions via their cargo. Here, the interaction between EVs derived from senescent (SEVs) and non-senescent (N-SEVs) fibroblasts and the immune system is investigated. Via endocytosis, SEVs are phagocytosed by monocytes, neutrophils, and B cells. Studies with the monocytic THP-1 cell line find that pretreatment with SEVs results in a 32% (p < 0.0001) and 66% (p < 0.0001) increase in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-α) production when compared to vehicle control or N-SEVs respectively. Interestingly, relative to vehicle control, THP-1 cells exposed to N-SEVs exhibit a 20% decrease in TNF-α secretion (p < 0.05). RNA sequencing reveals significant differences in gene expression in THP-1 cells treated with SEVs or N-SEVs, with vesicle-mediated transport and cell cycle regulation pathways featuring predominantly with N-SEV treatment, while pathways relating to SLITS/ROBO signaling, cell metabolism, and cell cycle regulation are enriched in THP-1 cells treated with SEVs. Proteomic analysis also reveals significant differences between SEV and N-SEV cargo. These results demonstrate that phagocytes and B cells uptake SEVs and drive monocytes toward a more proinflammatory phenotype upon LPS stimulation. SEVs may therefore contribute to the more proinflammatory immune response seen with aging.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400265"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492794","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}
Advanced biologyPub Date : 2024-12-01Epub Date: 2024-11-27DOI: 10.1002/adbi.202400334
Amira A Alakhdar, Sruthi Sivakumar, Rylee M Kopchak, Allison N Hunter, Fabrisia Ambrosio, Newell R Washburn
{"title":"Age-Related ECM Stiffness Mediates TRAIL Activation in Muscle Stem Cell Differentiation.","authors":"Amira A Alakhdar, Sruthi Sivakumar, Rylee M Kopchak, Allison N Hunter, Fabrisia Ambrosio, Newell R Washburn","doi":"10.1002/adbi.202400334","DOIUrl":"10.1002/adbi.202400334","url":null,"abstract":"<p><p>The stiffening of the extracellular matrix (ECM) with age hinders muscle regeneration by causing intrinsic muscle stem cell (MuSC) dysfunction through a poorly understood mechanism. Here, the study aims to study those age-related molecular changes in the differentiation of MuSCs due to age and/or stiffness. Hence, young and aged MuSCs are seeded onto substrates engineered to mimic a soft and stiff ECM microenvironment to study those molecular changes using single-cell RNA sequencing (scRNA). The trajectory of scRNA data of the MuSCs under four different conditions undergoing differentiation is analyzed as well as the active molecular pathways and transcription factors driving those differentiation fates. Data revealed the presence of a branching point within the trajectory leading to the emergence of an age-related fibroblastic population characterized by activation of the TNF-related apoptosis-inducing ligand (TRAIL) pathway, which is significantly activated in aged cells cultured on stiff substrates. Next, using the collagen cross-linking inhibitor β-aminopropionitrile (BAPN) in vivo, the study elucidates stiffness changes on TRAIL downstream apoptotic targets (caspase 8 and caspase 3) using immunostaining. TRAIL activity is significantly inhibited by BAPN in aged animals, indicating a complex mechanism of age-related declines in muscle function through inflammatory and apoptotic mediators.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400334"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724572","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}
Advanced biologyPub Date : 2024-12-01Epub Date: 2024-08-07DOI: 10.1002/adbi.202400201
Kejun Qi, Danqi Jia, Shengxi Zhou, Kun Zhang, Fangxia Guan, Minghao Yao, Xiaojie Sui
{"title":"Cryopreservation of Immune Cells: Recent Progress and Challenges Ahead.","authors":"Kejun Qi, Danqi Jia, Shengxi Zhou, Kun Zhang, Fangxia Guan, Minghao Yao, Xiaojie Sui","doi":"10.1002/adbi.202400201","DOIUrl":"10.1002/adbi.202400201","url":null,"abstract":"<p><p>Cryopreservation of immune cells is considered as a key enabling technology for adoptive cellular immunotherapy. However, current immune cell cryopreservation technologies face the challenges with poor biocompatibility of cryoprotection materials, low efficiency, and impaired post-thaw function, limiting their clinical translation. This review briefly introduces the adoptive cellular immunotherapy and the approved immune cell-based products, which involve T cells, natural killer cells and etc. The cryodamage mechanisms to these immune cells during cryopreservation process are described, including ice formation related mechanical and osmotic injuries, cryoprotectant induced toxic injuries, and other biochemical injuries. Meanwhile, the recent advances in the cryopreservation medium and freeze-thaw protocol for several representative immune cell type are summarized. Furthermore, the remaining challenges regarding on the cryoprotection materials, freeze-thaw protocol, and post-thaw functionality evaluation of current cryopreservation technologies are discussed. Finally, the future perspectives are proposed toward advancing highly efficient cryopreservation of immune cells.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400201"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900595","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}
Advanced biologyPub Date : 2024-12-01Epub Date: 2024-09-27DOI: 10.1002/adbi.202400293
Pengcheng Wang, Qiaozhen Huang, Yuejia Zhu, Liquan Chen, Kai Ye
{"title":"Fusobacterium Nucleatum Promotes Microsatellite Instability in Colorectal Carcinoma Through Up-regulation of miRNA-155-5p-Targeted Inhibition of MSH6 via the TLR4/NF-κB Signaling Pathway.","authors":"Pengcheng Wang, Qiaozhen Huang, Yuejia Zhu, Liquan Chen, Kai Ye","doi":"10.1002/adbi.202400293","DOIUrl":"10.1002/adbi.202400293","url":null,"abstract":"<p><p>Fusobacterium nucleatum (Fn) is significantly associated with poor prognosis in colorectal carcinoma (CRC), however, mechanisms of Fn in DNA mismatch repair (MMR) and microsatellite instability (MSI) in CRC have not been fully elucidated. Clinical samples are collected to analyze the relationship between Fn abundance and microsatellite stability. Tumor cells are treated with Fn to detect the expression of proteins related to toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88), mutS homolog 6 (MSH6), and nuclear factor-κB (NF-κB) signaling pathways, respectively. Combined with the prediction results from TargetScan, the regulatory role of microRNA upstream of MSH6 is demonstrated. The effect of this regulatory axis on CRC development is demonstrated using a nude mouse tumor model. Compared with microsatellite stability (MSS)-type CRC patients, MSI-type showed higher Fn abundance. Fn treatment of CRC cells activated TLR4/Myd88/NF-κB signaling pathway, transcriptionally activating miRNA-155-5p expression, thereby negatively regulating MSH6. Fn treatment accelerated the malignant progression of CRC in mice, and this process is inhibited by miRNA-155-5p antagomir. Fn in CRC upregulated miRNA-155-5p by activating TLR4/NF-κB signaling to inhibit MSH6, and this regulatory pathway may affect MSS of cancer cells.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400293"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339135","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}
Advanced biologyPub Date : 2024-12-01Epub Date: 2024-09-18DOI: 10.1002/adbi.202400113
Dallas E Altamirano, Eszter Mihaly, Jalissa D Emmens, Warren L Grayson
{"title":"Adipogenic-Myogenic Signaling in Engineered Human Muscle Grafts used to Treat Volumetric Muscle Loss.","authors":"Dallas E Altamirano, Eszter Mihaly, Jalissa D Emmens, Warren L Grayson","doi":"10.1002/adbi.202400113","DOIUrl":"10.1002/adbi.202400113","url":null,"abstract":"<p><p>Tissue-engineered muscle grafts (TEMGs) are a promising treatment for volumetric muscle loss (VML). In this study, human myogenic progenitors (hMPs) cultured on electrospun fibrin microfiber bundles and evaluated the therapeutic potential of engineered hMP TEMGs in the treatment of murine tibialis anterior (TA) VML injuries is employed. In vitro, the hMP TEMGs express mature muscle markers by 21 days. Upon implantation into VML injuries, the hMP TEMGs enable remarkable regeneration. To further promote wound healing and myogenesis, human adipose-derived stem/stromal cells (hASCs) as fibroadipogenic progenitor (FAP)-like cells with the potential to secrete pro-regenerative cytokines are incorporated. The impact of dose and timing of seeding the hASCs on in vitro myogenesis and VML recovery using hMP-hASC TEMGs are investigated. The hASCs increase myogenesis of hMPs when co-cultured at 5% hASCs: 95% hMPs and with delayed seeding. Upon implantation into immunocompromised mice, hMP-hASC TEMGs increase cell survival, collagen IV deposition, and pro-regenerative macrophage recruitment, but result in excessive adipose tissue growth after 28 days. These data demonstrate the interactions of hASCs and hMPs enhance myogenesis in vitro but there remains a need to optimize treatments to minimize adipogenesis and promote full therapeutic recovery following VML treatment.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400113"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278751","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}
Advanced biologyPub Date : 2024-12-01Epub Date: 2024-11-27DOI: 10.1002/adbi.202400431
Giacomo Domenici, Nuno F Lopes, Gonçalo Trindade, Isabella Ramella Gal, Joan Miret Minard, Sofia P Rebelo, Catarina Freitas, Nádia Duarte, Catarina Brito
{"title":"Assessing Novel Antibody-Based Therapies in Reconstructive 3D Cell Models of the Tumor Microenvironment.","authors":"Giacomo Domenici, Nuno F Lopes, Gonçalo Trindade, Isabella Ramella Gal, Joan Miret Minard, Sofia P Rebelo, Catarina Freitas, Nádia Duarte, Catarina Brito","doi":"10.1002/adbi.202400431","DOIUrl":"10.1002/adbi.202400431","url":null,"abstract":"<p><p>Targeted, combinatorial, and immunomodulatory therapies, such as antibody-drug conjugates (ADCs) and immunomodulatory antibodies (Abs), are powerful weapons against tumor cells and immune cells within the tumor microenvironment (TME). Therefore, the evaluation of such therapies should be conducted in pre-clinical models able to recapitulate the complex cellular and molecular crosstalk of the TME. To build-in critical hallmarks of the TME, a breast cancer heterotypic 3D cell model (3D-3) is devised using a microencapsulation strategy with an inert biomaterial (alginate) and agitation-based cultures. Both stromal and immune components are added to multicellular tumor spheroids, therefore fostering cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) immunomodulatory interactions. The potential of the methodology to assess Ab-based therapies is then addressed by employing a series of anti-HER2-based ADCs. ADCs induced tumor-cell specific cytotoxicity toward HER2+ breast cancer spheroids while sparing HER2-negative CAFs. In addition, an immunomodulatory blocking Ab against colony-stimulating factor 1 receptor (CSF1R) decreases the expression of immunosuppressive and anti-inflammatory markers in TAMs, like what is previously observed upon in vivo α-CSF1R administration. Collectively, the human TME-based 3D-3 cell model is a suitable tool to evaluate the anti-tumor and immunomodulatory potential of novel antibody-based therapies directed against TME targets, such as cancer cells and macrophages.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400431"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724575","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}
Advanced biologyPub Date : 2024-12-01DOI: 10.1002/adbi.202400264
Quan Gao, Youwei Xu, Massimiliano Galluzzi, Qi Xing, Jin Geng
{"title":"Enhanced Cancer Cell Specificity Through Combined Blue Light Therapy and Starvation Strategies.","authors":"Quan Gao, Youwei Xu, Massimiliano Galluzzi, Qi Xing, Jin Geng","doi":"10.1002/adbi.202400264","DOIUrl":"https://doi.org/10.1002/adbi.202400264","url":null,"abstract":"<p><p>In this study, the effectiveness of combining short-term starvation (STS or fasting) is investigated with blue light illumination therapy in delaying the progression of various types of cancer, including osteosarcoma, cervical, breast, liver carcinoma, and melanoma cancer in animal models. Moreover, the comparative analysis between cancerous (including HeLa, 143B, MDA-MB-231, and HepG2) and normal cell lines (including NCM460, HEKa, and L-O2), highlights the selectivity of the treatment's cytotoxic effects, favoring cancer cells while largely sparing normal cells. In HeLa cancer cells, treatment with the STS and blue light illumination combination resulted in increased phosphorylation of JNK and p38, which led to the activation of downstream signalling substrates, such as p53 and H2AX. This activation induced mitochondrial and nuclear damage, ultimately leading to tumor cell death. The combination treatment also caused metabolic disorders in tumor cells, which interfered with biomolecule availability and selectively induced lethal effects in tumor cells. Therefore, the combination treatment can be an effective strategy for eliminating cancer.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400264"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765433","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}
Advanced biologyPub Date : 2024-12-01Epub Date: 2024-08-20DOI: 10.1002/adbi.202400208
Lousineh Arakelian, Maëlys Léger, Sabrina Kellouche, Rémy Agniel, Patrick Bruneval, Jean Marc Allain, Valentino Caputo, Nicolas Gendron, Romane Gozlan, Rezlene Bargui, Augustin Vigouroux, Caroline Sansac, Mohamed Jarraya, Françoise Denoyelle, Jérôme Larghero, Briac Thierry
{"title":"A Clinical-Grade Partially Decellularized Matrix for Tracheal Replacement: Validation In Vitro and In Vivo in a Porcine Model.","authors":"Lousineh Arakelian, Maëlys Léger, Sabrina Kellouche, Rémy Agniel, Patrick Bruneval, Jean Marc Allain, Valentino Caputo, Nicolas Gendron, Romane Gozlan, Rezlene Bargui, Augustin Vigouroux, Caroline Sansac, Mohamed Jarraya, Françoise Denoyelle, Jérôme Larghero, Briac Thierry","doi":"10.1002/adbi.202400208","DOIUrl":"10.1002/adbi.202400208","url":null,"abstract":"<p><p>The management of extensive tracheal resection followed by circumferential replacement remains a surgical challenge. Numerous techniques are proposed with mixed results. Partial decellularization of the trachea with the removal of the mucosal and submucosal cells is a promising method, reducing immunogenicity while preserving the biomechanical properties of the final matrix. Despite many research protocols and proofs of concept, no standardized clinical grade protocol is described. Furthermore, local and systemic biointegration mechanisms of decellularized trachea are not well known. Therefore, in a translational research perspective, this work set up a partial tracheal decellularization protocol in line with Cell and Tissue Products regulations. Extensive characterization of the final product is performed in vitro and in vivo. The results show that the Partially Decellularized Trachea (PDT) is cell-free in the mucosa and submucosa, while the cartilage structure is preserved, maintaining the biomechanical properties of the trachea. When implanted in the muscle in vivo for 28 days, no systemic inflammation is observed, and locally, the PDT shows an excellent biointegration and vascularization. No signs of graft rejection are observed. These encouraging results confirmed the efficacy of the clinical grade PDT production protocol, which is an important step for future clinical applications.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400208"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003373","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}
Advanced biologyPub Date : 2024-11-27DOI: 10.1002/adbi.202400413
Min Xie, Huaiyuan Liang, Yuxuan Mao, Yuping Yao, Bingzhang Tian
{"title":"CBX3 Downregulates HLTF to Activate PI3K/AKT Signaling Promoting Cholangiocarcinoma.","authors":"Min Xie, Huaiyuan Liang, Yuxuan Mao, Yuping Yao, Bingzhang Tian","doi":"10.1002/adbi.202400413","DOIUrl":"https://doi.org/10.1002/adbi.202400413","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) is an aggressive cancer with poor response to chemotherapy or radiation, necessitating novel therapeutic approaches. Epigenetic regulation, which is reversible, plays a significant role in cancer progression. CBX3 (HP1γ), a key heterochromatin protein, regulates gene expression by interacting with histone H3 lysine 9 trimethyl (H3K9me3) markers. While CBX3 is linked to tumor progression in various cancers, its role in CCA remains unclear. This study reveals that CBX3 and H3K9me3 enrich the HLTF promoter, a gene involved in chromatin remodeling and DNA repair. HLTF is often inactivated by hypermethylation in other cancers, suggesting tumor-suppressive properties. Depleting CBX3 in CCA cells elevates HLTF expression, reducing proliferation, while HLTF silencing reverses this effect. Furthermore, HLTF overexpression inhibits PI3K-AKT signaling activated by CBX3. These findings suggest CBX3 promotes CCA progression by suppressing HLTF expression.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400413"},"PeriodicalIF":3.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724605","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}