Translational Oncology最新文献

{"title":"TRIM6 promotes glioma malignant progression by enhancing FOXO3A ubiquitination and degradation.","authors":"Jingpeng Guo, Ji Wang, Peng Zhang, Ping Wen, Shoudan Zhang, Xuchen Dong, Jun Dong","doi":"10.1016/j.tranon.2024.101999","DOIUrl":"10.1016/j.tranon.2024.101999","url":null,"abstract":"<p><strong>Purpose: </strong>TRIM6, an E3 ubiquitin ligase with tripartite motif, directly targets protein substrates for degradation through ubiquitination. Studies have shown that TRIM6 plays a significant role in tumor development in various human malignancies. Thus, the aim of this study was to investigate the importance of TRIM6 and its associated mechanism in promoting the progression of glioma.</p><p><strong>Methods: </strong>The expression of TRIM6 and its prognostic value in glioma patients were collected from the TCGA and CGGA databases. The effects of TRIM6 on glioma were investigated in vitro by CCK8, colony formation, wound healing, and transwell assays. Co-IP and western blot analysis were used to detect the interaction between TRIM6 and FOXO3A. The effects of TRIM6 were verified in vivo in subcutaneously xenograft models, and tumor size, and immunohistochemical changes were observed.</p><p><strong>Results: </strong>Our analysis of TRIM6 expression in glioma tissues revealed a high level of expression, and the heightened expression of TRIM6 showed a positive correlation with the unfavorable prognosis among glioma/GBM patients. Through loss-of-function and gain-of-function experiments, we observed a profound impact on the proliferation, invasion, and migration abilities of glioma cells both in vitro and in vivo upon deletion of TRIM6. Conversely, the overexpression of TRIM6 intensified the malignant characteristics of glioma. Additionally, our findings revealed a significant interaction between TRIM6 and FOXO3A, wherein TRIM6 contributed to the destabilization of FOXO3A protein by promoting its ubiquitination and subsequent degradation. Experiments conducted in the rescue study affirmed that the promotion of glioma cell proliferation, invasion, and migration is facilitated by TRIM6 through the suppression of FOXO3A protein levels.</p><p><strong>Conclusions: </strong>These observations imply that the TRIM6-FOXO3A axis could potentially serve as an innovative focus for intervening in glioma.</p>","PeriodicalId":23244,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959090","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":"CREB3 facilitates Donafenib resistance in hepatocellular carcinoma cells via the LSD1/CoREST/p65 axis by transcriptionally activating long noncoding RNA ZFAS1","authors":"Xunbo Hou, Qiannan Xu, Ruibao Liu","doi":"10.1016/j.tranon.2023.101684","DOIUrl":"https://doi.org/10.1016/j.tranon.2023.101684","url":null,"abstract":"<h3>Objective</h3><p>Drug resistance greatly limits the therapeutic effect of a drug. This study aimed to explore the role of long noncoding RNA ZFAS1 in Donafenib resistance of hepatocellular carcinoma (HCC) cells.</p><h3>Methods</h3><p>The expression of CREB3, ZFAS1, and p65 in HCC cell lines was measured by RT-qPCR and western blotting. After transfection with sh-ZFAS1, sh-CREB3, or sh-CREB3 + oe-p65 in Donafenib-resistent (DR) HCC cell lines, the transfection efficiency was evaluated by RT-qPCR and western blotting. The proliferation and IC₅₀ to Donafenib of HCC cell lines was examined by MTT assay. Cell proliferation and apoptosis were examined by colony formation and flow cytometry assays. Then, the correlation amongst CREB3, ZFAS1, LSD1/CoREST, and p65 was analysed by ChIP, dual-luciferase reporter gene, and RIP assays.</p><h3>Results</h3><p>ZFAS1, CREB3, and p65 were upregulated in HepG2-DR and Huh7-DR cells. Silencing of ZFAS1 or CREB3 enhanced the sensitivity of HCC cells to Donafenib, inhibited cell proliferation and IC₅₀, and increased cell apoptosis, which were reversed by p65 overexpression. Mechanistically, CREB3 bound to ZFAS1 promoter to augment ZFAS1 transcriptional expression, and ZFAS1 recruited LSD1/CoREST to the p65 promoter region to decrease H3K4 methylation and elevate p65 transcriptional expression.</p><h3>Conclusion</h3><p>CREB3 overexpression contributed to Donafenib resistance in HCC cells by activating the ZFAS1/p65 axis.</p>","PeriodicalId":23244,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138519819","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}

{"title":"New insights into possible HDAC inhibitor resistance in DLBCL - Comment on 'defining cellular responses to HDAC-selective inhibitors reveals that efficient targeting of HDAC3 is required to elicit cytotoxicity and overcome naïve resistance to pan-HDACi in diffuse large B cell lymphoma' by Havas et al.","authors":"Tobias Kiesslich, Christian Mayr, Dino Bekric, Daniel Neureiter","doi":"10.1016/j.tranon.2023.101820","DOIUrl":"https://doi.org/10.1016/j.tranon.2023.101820","url":null,"abstract":"Abstract not available","PeriodicalId":23244,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138519838","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}

{"title":"LOX rises as a potential survival biomarker: A commentary on “Identification of LOX as a candidate prognostic biomarker in Glioblastoma multiforme” by Liu et al.","authors":"Eduardo Silva-Pavez, Hery Urra","doi":"10.1016/j.tranon.2023.101777","DOIUrl":"https://doi.org/10.1016/j.tranon.2023.101777","url":null,"abstract":"","PeriodicalId":23244,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44375114","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}

{"title":"Early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis","authors":"Eun Young Kim, Y. Cha, Sang Hoon Lee, Sukin Jeong, Y. Choi, D. Moon, Sungsoo Lee, Y. Chang","doi":"10.21203/rs.3.rs-735382/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-735382/v1","url":null,"abstract":"Highlights • Tregs lead immune-evasive TME of early lung cancer of never smoker.• Depletion of γδT and NK cells and infiltration of B cells begins in early TME.• Early lung cancer cells were characterized by dysregulated surfactant pathway.• CAFs show enrichment of gene sets that inhibit vascular formation. In tumor tissue, tip-like endothelial cells begin to be replaced with immature ones.","PeriodicalId":23244,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2021-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43961501","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}

{"title":"Mining database for the expression and clinical significance of STAT family in head and neck squamous cell carcinomas.","authors":"Haosheng Ni,&nbsp;Hui Sun,&nbsp;Miaosen Zheng,&nbsp;Tingting Bian,&nbsp;Jian Liu,&nbsp;Xiaoli Li,&nbsp;Jianguo Zhang,&nbsp;Yifei Liu","doi":"10.1016/j.tranon.2020.100976","DOIUrl":"https://doi.org/10.1016/j.tranon.2020.100976","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinomas (HNSC) are among the most common malignant tumors with high incidence, relapse, and mortality rate. STAT proteins are implicated in various biological processes, including cell proliferation, metastasis, and immune regulation.</p><p><strong>Method: </strong>Various bioinformatics tools were used to explore the role of the STAT family in HNSC.</p><p><strong>Result: </strong>The mRNA levels of STAT1/2/4/5A/6 were significantly upregulated in HNSC tissues. The levels of STAT1/2/4/5A/6 could be used for the detection of HNSC. HNSC patients with a high level of STAT5A had a poor overall survival and relapse-free survival. A moderate to high correlation was obtained between the STAT family and HNSC. Genetic alteration revealed that STAT1/2/3/4/5A/5B/6 were altered in 6%, 5%, 7%, 8%, 6%, 6%, and 4% of the queried TCGA HNSC samples, respectively. Immune infiltrations analysis suggested a significant association between STAT5A expression and abundance of specific immune cells. Further, copy number alteration of STAT5A could certainly inhibit infiltration level. Moreover, a close correlation was obtained between STAT5A level and the expression of immune markers in HNSC. Several kinase targets and transcription factor targets of STAT5A in HNSC were also identified. Enrichment analysis suggested that STAT5A and co-expression genes were mainly responsible for adaptive immune response, T cell activation, cytokine-cytokine receptor interaction, chemokine signaling pathway, cell-adhesion molecules, and ribosome and RNA transport.</p><p><strong>Conclusion: </strong>Our results provided additional data for the expression and clinical significance of the STAT family in HNSC, and further study should be performed to verify these.</p>","PeriodicalId":23244,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tranon.2020.100976","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39114656","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":"Endogenous retroviruses expressed in human tumours cannot be used as targets for anti-tumour vaccines.","authors":"Joachim Denner","doi":"10.1016/j.tranon.2020.100941","DOIUrl":"https://doi.org/10.1016/j.tranon.2020.100941","url":null,"abstract":"<p><p>Many tumour cells express on their surface proteins of endogenous retroviruses (ERVs) and there are suggestions to use these retroviral antigens as target for anti-tumour vaccines. However, until now there is no convincing data showing that this strategy works, in contrast, there are considerations suggesting that this strategy may be harmful if applied.</p>","PeriodicalId":23244,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tranon.2020.100941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38627761","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":"Get rid of pancreatic cancer by inhibiting garbage disposal?: Comment on \"UAE1 Inhibition mediates the unfolded protein response, DNA damage and caspase-dependent cell death in pancreatic cancer\" by Rehemtulla et al.","authors":"Claudia Geismann,&nbsp;Alexander Arlt","doi":"10.1016/j.tranon.2020.100968","DOIUrl":"https://doi.org/10.1016/j.tranon.2020.100968","url":null,"abstract":"","PeriodicalId":23244,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tranon.2020.100968","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38693336","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":"Rewiring Tumor Cell State in Cancer Therapy: Comment on '9-cis-UAB30, a Novel Rexinoid Agonist, Decreases Tumorigenicity and Cancer Cell Stemness of Human Neuroblastoma Patient-Derived Xenografts' by 'Elizabeth Beierle et al.'","authors":"Abhishek A Chakraborty","doi":"10.1016/j.tranon.2020.100967","DOIUrl":"https://doi.org/10.1016/j.tranon.2020.100967","url":null,"abstract":"","PeriodicalId":23244,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tranon.2020.100967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38677863","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":"Thymic function affects breast cancer development and metastasis by regulating expression of thymus secretions PTMα and Tβ15b1.","authors":"Dongling Shi,&nbsp;Yanmei Shui,&nbsp;Xie Xu,&nbsp;Kai He,&nbsp;Fengqing Yang,&nbsp;Jianli Gao","doi":"10.1016/j.tranon.2020.100980","DOIUrl":"https://doi.org/10.1016/j.tranon.2020.100980","url":null,"abstract":"<p><p>Breast cancer is currently one of the most common malignant tumors in women. Our previous research found that thymic dysfunction has a certain relationship with the occurrence and development of breast cancer. In order to explore whether the functional status of thymus is related to the development and metastasis of breast cancer, we use BALB/c wild type mice (BALB wt), BALB/c nude mice (BALB nu), BALB wt mice implanted with 4T1 cells (wt 4T1), BALB nu with 4T1 (nu 4T1), D-galactose treatment wt 4T1 mice (D-Gal), Thymalfasin treatment wt 4T1 mice (Tα1), Cyclophosphamide treatment wt 4T1 mice (CTX), Doxorubicin treatment wt 4T1 mice (Dox) in the research. As a result, nu 4T1, D-Gal and DOX had earlier lung metastases. Gene chip results showed that PTMα and Tβ15b1 were the most up-regulated and down-regulated genes in thymosin-related genes, respectively. Overexpression or silencing of PTMα and Tβ15b1 genes did not affect the proliferation of 4T1 cells. PTMα gene silenced, cell migration and invasion ability enhanced, while PTMα gene overexpression, the cell invasion ability weaken. In vivo, PTMα gene overexpression promotes tumor growth and lung metastasis in the early stage, but has no significant effect in the later stage. Tβ15b1 overexpression also promotes tumor growth in the early stage, but suppresses in the later stage. Tβ15b1 gene silencing inhibits tumor lung metastasis. Thus, our findings demonstrated that thymic function affects breast cancer development and metastasis by regulating expression of thymus secretions PTMα and Tβ15b1. Our study provided new directions for breast cancer therapy.</p>","PeriodicalId":23244,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.tranon.2020.100980","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39114652","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}