Cell and Bioscience最新文献

{"title":"Single‑cell RNA sequencing analysis of human embryos from the late Carnegie to fetal development","authors":"Chengniu Wang, Xiaorong Wang, Wenran Wang, Yufei Chen, Hanqing Chen, Weizhen Wang, Taowen Ye, Jin Dong, Chenliang Sun, Xiaoran Li, Chunhong Li, Jiaying Li, Yong Wang, Xingmei Feng, Hongping Ding, Dawei Xu, Jianwu Shi","doi":"10.1186/s13578-024-01302-9","DOIUrl":"https://doi.org/10.1186/s13578-024-01302-9","url":null,"abstract":"The cell development atlas of transition stage from late Carnegie to fetal development (7–9 weeks) remain unclear. It can be seen that the early period of human embryos (7–9 weeks) is a critical research gap. Therefore, we employed single‑cell RNA sequencing to identify cell types and elucidate differentiation relationships. The single‑cell RNA sequencing analysis determines eighteen cell clusters in human embryos during the 7–9 weeks period. We uncover two distinct pathways of cellular development and differentiation. Initially, mesenchymal progenitor cells differentiated into osteoblast progenitor cells and neural stem cells, respectively. Neural stem cells further differentiated into neurons. Alternatively, multipotential stem cells differentiated into adipocyte, hematopoietic stem cells and neutrophil, respectively. Additionally, COL1A2-(ITGA1 + ITGB1) mediated the cell communication between mesenchymal progenitor cells and osteoblast progenitor cells. NCAM1-FGFR1 facilitated the cell communication between mesenchymal progenitor cells and neural stem cells. Notably, NCAM1-NCAM1 as a major contributor mediated the cell communication between neural stem cells and neurons. Moreover, CGA-FSHR simultaneously mediated the communication between multipotential stem cells, adipocyte, hematopoietic stem cells and neutrophil. Distinct cell clusters activated specific transcription factors such as HIC1, LMX1B, TWIST1, and et al., which were responsible for their specific functions. These coregulators, such as HOXB13, VSX2, PAX5, and et al., may mediate cell development and differentiation in human embryos. We provide the cell development atlas for human embryos (7–9 weeks). Two distinct cell development and differentiation pathways are revealed.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"26 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in predictive biomarkers associated with immunotherapy in extensive-stage small cell lung cancer","authors":"Tong Chen, Mingzhao Wang, Yanchao Chen, Yang Cao, Yutao Liu","doi":"10.1186/s13578-024-01283-9","DOIUrl":"https://doi.org/10.1186/s13578-024-01283-9","url":null,"abstract":"Small cell lung cancer (SCLC) is a highly malignant and poor-prognosis cancer, with most cases diagnosed at the extensive stage (ES). Amidst a landscape marked by limited progress in treatment modalities for ES-SCLC over the past few decades, the integration of immune checkpoint inhibitors (ICIs) with platinum-based chemotherapy has provided a milestone approach for improving prognosis, emerging as the new standard for initial therapy in ES-SCLC. However, only a minority of SCLC patients can benefit from ICIs, which frequently come with varying degrees of immune-related adverse events (irAEs). Therefore, it is crucial to investigate predictive biomarkers to screen potential beneficiaries of ICIs, mitigate the risk of side effects, and improve treatment precision. This review summarized potential biomarkers for predicting ICI response in ES-SCLC, with a primary focus on markers sourced from tumor tissue or peripheral blood samples. The former mainly included PD-L1 expression, tumor mutational burden (TMB), along with cellular or molecular components related to the tumor microenvironment (TME) and antigen presentation machinery (APM), molecular subtypes of SCLC, and inflammatory gene expression profiles. Circulating biomarkers predominantly comprised circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), cytokines, plasma autoantibodies, inflammation-related parameters, and blood TMB. We synthesized and analyzed the research progress of these potential markers. Notably, investigations into PD-L1 expression and TMB have been the most extensive, exhibiting preliminary predictive efficacy in salvage immunotherapy; however, consistent conclusions have yet to be reached across studies. Additionally, novel predictive markers developed based on TME composition, APM, transcriptomic and genomic features provide promising tools for precision immunotherapy. Circulating biomarkers offer the advantages of convenience, non-invasiveness, and a comprehensive reflection of tumor molecular characteristics. They may serve as alternative options for predicting immunotherapy efficacy in SCLC. However, there is a scarcity of studies, and the significant heterogeneity in research findings warrants attention.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"12 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma","authors":"Yaqun Li, Furan Wang, Zikai Geng, Tianye He, Yun Song, Jian Wu, Bin Wang","doi":"10.1186/s13578-024-01298-2","DOIUrl":"https://doi.org/10.1186/s13578-024-01298-2","url":null,"abstract":"Hepatitis B virus (HBV) infection can exacerbate liver disease progression through multiple mechanisms, eventually leading to hepatocellular carcinoma (HCC). HBV-encoded oncogene X protein (HBx), a key regulatory protein of HBV infection, serves as a positive regulator of hepatocarcinogenesis. The indispensability of the M2 subunit of ribonucleotide-diphosphate reductase (RRM2) lies in its role in facilitating DNA replication and repair processes. In our previous investigation, it was postulated that the gene RRM2 exhibits elevated expression levels in several categories of malignant tumors, particularly in HBV-related HCC. Additionally, it was observed that RRM2 is present within protein complexes that are centered on HBx. In the present investigation, the objective of this work was to investigate the potential relationship between the elevated expression of RRM2 in HBV-related HCC and the influence of HBx on this expression. The study attempted to determine the specific mechanism by which RRM2 is implicated in the promotion of hepatocarcinogenesis by HBx. There have been multiple scholarly proposals suggesting that the induction of autophagy by HBx is a significant intermediary factor in the development of HCC. However, the precise carcinogenic function of HBx-induced autophagy remains a subject of debate. This work initially investigated the impact of suppressing cellular autophagy on the malignant biological behaviors of HBx-promoted cells using an in vitro cellular model. The findings revealed that the suppression of cellular autophagy partially disrupted the oncogenic effects of HBx. In light of this, we proceeded to conduct more investigations into the regulatory association between RRM2 and HBx-induced autophagy in the upstream-downstream context. Our data indicate that HBx proteins increase the expression of RRM2. Suppression of RRM2 expression not only hinders HBx-induced autophagy, but also worsens the cellular G1/S blockage and reduces the HBx-induced malignant growth of hepatocellular carcinoma tumors, while stimulating apoptosis. Therefore, we hypothesised that RRM2 is a potential downstream target of HBx-induced hepatocarcinogenesis, and mining the oncogenic mechanism of RRM2 is significant in exploring the preventive treatment of HBV-related HCC.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"34 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting stress induction of GRP78 by cardiac glycoside oleandrin dually suppresses cancer and COVID-19.","authors":"Dat P Ha, Woo-Jin Shin, Ze Liu, Michael E Doche, Roy Lau, Nektaria Maria Leli, Crystal S Conn, Mariangela Russo, Annalisa Lorenzato, Constantinos Koumenis, Min Yu, Shannon M Mumenthaler, Amy S Lee","doi":"10.1186/s13578-024-01297-3","DOIUrl":"10.1186/s13578-024-01297-3","url":null,"abstract":"<p><strong>Background: </strong>Despite recent therapeutic advances, combating cancer resistance remains a formidable challenge. The 78-kilodalton glucose-regulated protein (GRP78), a key stress-inducible endoplasmic reticulum (ER) chaperone, plays a crucial role in both cancer cell survival and stress adaptation. GRP78 is also upregulated during SARS-CoV-2 infection and acts as a critical host factor. Recently, we discovered cardiac glycosides (CGs) as novel suppressors of GRP78 stress induction through a high-throughput screen of clinically relevant compound libraries. This study aims to test the possibility that agents capable of blocking stress induction of GRP78 could dually suppress cancer and COVID-19.</p><p><strong>Results: </strong>Here we report that oleandrin (OLN), is the most potent among the CGs in inhibiting acute stress induction of total GRP78, which also results in reduced cell surface and nuclear forms of GRP78 in stressed cells. The inhibition of stress induction of GRP78 is at the post-transcriptional level, independent of protein degradation and autophagy and may involve translational control as OLN blocks stress-induced loading of ribosomes onto GRP78 mRNAs. Moreover, the human Na⁺/K⁺-ATPase α3 isoform is critical for OLN suppression of GRP78 stress induction. OLN, in nanomolar range, enhances apoptosis, sensitizes colorectal cancer cells to chemotherapeutic agents, and reduces the viability of patient-derived colon cancer organoids. Likewise, OLN, suppresses GRP78 expression and impedes tumor growth in an orthotopic breast cancer xenograft model. Furthermore, OLN blocks infection by SARS-CoV-2 and its variants and enhances existing anti-viral therapies. Notably, GRP78 overexpression mitigates OLN-mediated cancer cell apoptotic onset and suppression of virus release.</p><p><strong>Conclusion: </strong>Our findings validate GRP78 as a target of OLN anti-cancer and anti-viral activities. These proof-of-principle studies support further investigation of OLN as a readily accessible compound to dually combat cancer and COVID-19.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"115"},"PeriodicalIF":6.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YIPF2 regulates genome integrity.","authors":"Xiao Zhang, Tao Wang","doi":"10.1186/s13578-024-01300-x","DOIUrl":"10.1186/s13578-024-01300-x","url":null,"abstract":"<p><p>Understanding of the mechanisms for genome integrity maintenance can help in developing effective intervention strategies to combat aging. A whole-genome RNAi screen was conducted to identify novel factors involved in maintaining genome stability. The potential target genes identified in the screening are related to the cell cycle, proteasome, and spliceosomes. Unexpectedly, the Golgi protein YIPF2 has been found to play a critical role in maintaining genome stability. The depletion of YIPF2 hinders the process of homologous recombination (HR) repair, which then triggers DNA damage response mechanisms, ultimately leading to cellular senescence. The overexpression of YIPF2 facilitated cellular recovery from DNA damage induced by chemotherapy agents or replicative senescence-associated DNA damage. Our findings indicate that only the intact Golgi apparatus containing YIPF2 provides a protective effect on genome integrity.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"114"},"PeriodicalIF":6.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of extracellular vesicle-associated proteins in the progression, diagnosis, and treatment of hepatocellular carcinoma.","authors":"Yao-Ge Liu, Shi-Tao Jiang, Jun-Wei Zhang, Han Zheng, Lei Zhang, Hai-Tao Zhao, Xin-Ting Sang, Yi-Yao Xu, Xin Lu","doi":"10.1186/s13578-024-01294-6","DOIUrl":"10.1186/s13578-024-01294-6","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by difficulties in early diagnosis, prone to distant metastasis, and high recurrence rates following surgery. Extracellular vesicles (EVs) are a class of cell-derived particles, including exosomes, characterized by a phospholipid bilayer. They serve as effective carriers for intercellular communication cargo, including proteins and nucleic acids, and are widely involved in tumor progression. They are being explored as potential tumor biomarkers and novel therapeutic avenues. We provide a brief overview of the biogenesis and characteristics of EVs to better understand their classification standards. The focus of this review is on the research progress of EV-associated proteins in the field of HCC. EV-associated proteins are involved in tumor growth and regulation in HCC, participate in intercellular communication within the tumor microenvironment (TME), and are implicated in events including angiogenesis and epithelial-mesenchymal transition (EMT) during tumor metastasis. In addition, EV-associated proteins show promising diagnostic efficacy for HCC. For the treatment of HCC, they also demonstrate significant potential including enhancing the efficacy of tumor vaccines, and as targeting cargo anchors. Facing current challenges, we propose the future directions of research in this field. Above all, research on EV-associated proteins offers the potential to enhance our comprehension of HCC and offer novel insights for developing new treatment strategies.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"113"},"PeriodicalIF":6.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deubiquitinase USP10 promotes osteosarcoma autophagy and progression through regulating GSK3β-ULK1 axis.","authors":"Zuxi Feng, Yanghuan Ou, Xueqiang Deng, Minghao Deng, Xiaohua Yan, Leifeng Chen, Fan Zhou, Liang Hao","doi":"10.1186/s13578-024-01291-9","DOIUrl":"10.1186/s13578-024-01291-9","url":null,"abstract":"<p><strong>Background: </strong>Deubiquitinating enzymes (DUBs) are pivotal in maintaining cell homeostasis by regulating substrate protein ubiquitination in both healthy and cancer cells. Ubiquitin-specific protease 10 (USP10) belongs to the DUB family. In this study, we investigated the clinical and pathological significance of USP10 and Unc-51-like autophagy activating kinase 1 (ULK1) in osteosarcoma (OS), as well as the mechanism of USP10 action in ULK1-mediated autophagy and disease progression.</p><p><strong>Results: </strong>The analysis of OS and adjacent normal tissues demonstrated that USP10 and ULK1 were significantly overexpressed in OS, and a positive association between their expression and malignant properties was observed. USP10 knockdown in OS cells reduced ULK1 mRNA and protein expression, whereas USP10 overexpression increased ULK1 mRNA and protein expression. In vitro experiments showed that USP10 induced autophagy, cell proliferation, and invasion by enhancing ULK1 expression in OS cell lines. Furthermore, we found that the regulation of ULK1-mediated autophagy, cell proliferation, and invasion in OS by USP10 was dependent on glycogen synthase kinase 3β (GSK3β) activity. Mechanistically, USP10 promoted ULK1 transcription by interacting with and stabilising GSK3β through deubiquitination, which, in turn, increased the activity of the ULK1 promoter, thereby accelerating OS progression. Using a xenograft mouse model, we showed that Spautin-1, a small-molecule inhibitor targeting USP10, significantly reduced OS development, with its anti-tumour activity significantly enhanced when combined with the chemotherapeutic agent cisplatin.</p><p><strong>Conclusion: </strong>Collectively, we demonstrated that the USP10-GSK3β-ULK1 axis promoted autophagy, cell proliferation, and invasion in OS. The findings imply that targeting USP10 may offer a promising therapeutic avenue for treating OS.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"111"},"PeriodicalIF":6.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell and spatial sequencing identifies senescent and germinal tumor cells in adamantinomatous craniopharyngiomas.","authors":"Xianlong Wang, Jincheng Lin, Hongxing Liu, Chuan Zhao, Zhiwei Tu, Dapeng Xu, En Zhang, Zhongqing Zhou, Xueling Qi, Xingfu Wang, Zhixiong Lin","doi":"10.1186/s13578-024-01299-1","DOIUrl":"10.1186/s13578-024-01299-1","url":null,"abstract":"<p><p>Adamantinomatous craniopharyngioma (ACP) is a clinically aggressive tumor without effective treatment method. Previous studies proposed a paracrine tumorigenesis model, in which oncogenic β-catenin induces senescence in pituitary stem cells and the senescent cells lead the formation of paracrine tumors through secretion of pro-tumorigenic factors. However, there lacks characterization on senescent cells in ACPs. Here, we profiled 12 ACPs with single-cell RNA and TCR-sequencing to elucidate the cellular atlas in ACPs and 3 of them were also subject to spatial sequencing to localize different subpopulations of the tumor cells. In total, we obtained the transcriptome profiles of 70,682 cells. Tumor cells, which were unambiguously identified through the cellular mutation status of the driver CTNNB1 mutations, were clustered into 6 subsets. The whorl-like cluster (WC) cells show distinct molecular features from the other tumor cells and the palisading epithelium (PE) cells consists of a proliferating subset. Other than typical PE and WC, we identified two novel subpopulations of the tumor cells. In one subpopulation, the cells express a high level of cytokines, e.g., FDCSP and S100A8/A9, and are enriched with the senescence-associated secretory phenotype (SASP) factors. Hematoxylin and eosin staining reveals that these SASP cells lack an ordered structures and their nuclei are elongated. In the other subpopulation, the cell sizes are small and they are tightly packed together with an unusual high density expressing a high level of mitochondrial genes (median 10.9%). These cells are the origin of the tumor developmental trajectories revealed by RNA velocity and pseudo-time analysis. Single-cell RNA and TCR analysis reveals that some ACPs are infiltrated with clonally expanded cytotoxic T cells. We propose a hypothesis that WC and PE are formed via different negative regulation mechanisms of the overactivated WNT/β-catenin signaling which provides a new understanding on the tumorigenesis of ACPs. The study lays a foundation for future studies on targeting senescent cells in ACPs with senolytic compounds or other therapeutic agents.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"112"},"PeriodicalIF":6.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"V1bR enhances glucose-stimulated insulin secretion by paracrine production of glucagon which activates GLP-1 receptor.","authors":"Ying Yun, Shimeng Guo, Xin Xie","doi":"10.1186/s13578-024-01288-4","DOIUrl":"10.1186/s13578-024-01288-4","url":null,"abstract":"<p><strong>Background: </strong>Arginine vasopressin (AVP) has been reported to regulate insulin secretion and glucose homeostasis in the body. Previous study has shown that AVP and its receptor V1bR modulate insulin secretion via the hypothalamic-pituitary-adrenal axis. AVP has also been shown to enhance insulin secretion in islets, but the exact mechanism remains unclear.</p><p><strong>Results: </strong>In our study, we unexpectedly discovered that AVP could only stimulates insulin secretion from islets, but not β cells, and AVP-induced insulin secretion could be blocked by V1bR selective antagonist. Single-cell transcriptome analysis identified that V1bR is only expressed by the α cells. Further studies indicated that activation of the V1bR stimulates the α cells to secrete glucagon, which then promotes glucose-dependent insulin secretion from β cells in a paracrine way by activating GLP-1R but not GCGR on these cells.</p><p><strong>Conclusions: </strong>Our study revealed a crosstalk between α and β cells initiated by AVP/V1bR and mediated by glucagon/GLP-1R, providing a mechanism to develop new glucose-controlling therapies targeting V1bR.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"110"},"PeriodicalIF":6.1,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MST1R-targeted therapy in the battle against gallbladder cancer.","authors":"Wei Wang, Chao Huang, Li Zhang, Liqin Yu, Yangming Liu, Puxiongzhi Wang, Rongmu Xia","doi":"10.1186/s13578-024-01290-w","DOIUrl":"10.1186/s13578-024-01290-w","url":null,"abstract":"<p><strong>Background: </strong>Gallbladder cancer (GBC) is characterized by high mortality rate. Our study sought therapeutic candidates for GBC.</p><p><strong>Results: </strong>Bioinformatics analysis identified significant upregulation of MST1R in GBC. In vitro experiments demonstrated that the MST1R inhibitor MGCD-265 effectively restrained GBC cell proliferation at lower concentrations. Additionally, it induced cycle arrest and apoptosis in GBC cells in a dose-dependent manner. Mouse models exhibited that MGCD-265 treatment significantly diminished the proliferative capacity of GBC-SD cells. Transcriptomics sequencing revealed significant transcriptome alterations, with 200 transcripts upregulated and 883 downregulated. KEGG and GO analyses highlighted enrichment in processes like cell adhesion and pathways such as protein digestion and absorption. Downstream genes analysis identified JMJD6 upregulation post-MGCD-265 treatment. In vivo experiments confirmed that combining MGCD-265 with the JMJD6 inhibitor SKLB325 enhanced the anticancer effect against GBC.</p><p><strong>Conclusion: </strong>Overall, targeting MST1R and its downstream genes, particularly combining MGCD-265 with SKLB325, holds promise as a therapeutic strategy for GBC.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"109"},"PeriodicalIF":6.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}