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We are analyzing https://jeccr.biomedcentral.com/articles/10.1186/s13046-022-02266-9.

Title:
HDAC7 promotes NSCLC proliferation and metastasis via stabilization by deubiquitinase USP10 and activation of β-catenin-FGF18 pathway | Journal of Experimental & Clinical Cancer Research | Full Text
Description:
Background Histone deacetylases (HDACs) play crucial roles in cancers, but the role and mechanism of HDAC7 in NSCLC have not been fully understood. Methods A total of 319 patients with non-small cell lung cancer (NSCLC) who underwent surgery were enrolled in this study. Immunohistochemistry and Kaplan–Meier survival analysis were performed to investigate the relationship between HDAC7, fibroblast growth factor 18 (FGF18) expression, and clinicopathologic characteristics. Cell functional experiments were implemented both in vivo and in vitro to investigate the effects on NSCLC cell proliferation and metastasis. Recombinant lentivirus–meditated in vivo gene overexpression or knockdown, real-time polymerase chain reaction (PCR), western blotting, and coimmunoprecipitation assays were applied to clarify the underlying molecular mechanism of HDAC7 in promoting NSCLC progression. Results The elevated expression of HDAC7 or FGF18 was positively correlated with poor prognosis, tumor–node–metastasis (TNM) stage, and tumor differentiation of NSCLC patients. NSCLC patients with co-expressed HDAC7 and FGF18 suffered the worst prognosis. HDAC7 overexpression promoted NSCLC proliferation and metastasis by upregulating FGF18. Conversely, overexpression of FGF18 reversed the attenuated ability in tumor growth and metastasis mediated by downregulating HDAC7. In terms of mechanism, our results suggested that the interaction of HDAC7 with β-catenin caused decreased β-catenin acetylation level at Lys49 and decreased phosphorylation level at Ser45. As a consequence, the HDAC7-mediated posttranslational modification of β-catenin facilitated nuclear transfer and activated FGF18 expression via binding to TCF4. Furthermore, deubiquitinase USP10 interacted with and stabilized HDAC7. The suppression of USP10 significantly accelerated the degradation of HDAC7 and weakened NSCLC growth and migration. Conclusions Our findings reveal that HDAC7 promotes NSCLC progression through being stabilized by USP10 and activating the β-catenin-FGF18 pathway. Targeting this novel pathway may be a promising strategy for further developments in NSCLC therapy.
Website Age:
25 years and 10 months (reg. 1999-08-06).

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Keywords {šŸ”}

hdac, nsclc, fgf, cells, expression, cell, fig, cancer, usp, βcatenin, analysis, article, overexpression, google, scholar, metastasis, representative, patients, assay, lung, tumor, data, cas, proliferation, protein, western, significantly, results, tissues, knockdown, blotting, control, images, growth, levels, showed, progression, group, promotes, prognosis, tumors, pathway, study, correlated, upregulated, found, zhang, role, survival, performed,

Topics {āœ’ļø}

beta-catenin/t-cell factor complex hdac7-β-catenin–fgf18 regulatory axis mir-29b/hdac4 epigenetic loop springer nature wnt/β-catenin signaling pathway aberrant wnt/β-catenin signaling hdac7-β-catenin–fgf18 pathway mir-4465-epha2 signaling axis enzyme-linked immunosorbent assay kaplan–meier plotter database enzyme-linked immunosorbent assays wnt/β-catenin signaling paraffin-embedded tissue microarray β-catenin related genes kaplan–meier survival analysis β-catenin/tcf4 complex β-catenin–tcf4 complex pseudo-colored luminescent images tcf-responsive promoter reporter β-catenin-fgf18 pathway crucial pro-proliferative factor relative top/fop ratio cell cycle–related proteins additional information publisher' wild-type p53 fop luciferase activity protein–protein interaction surfaces hdac7-enhanced nsclc progression raw rna-seq data β-catenin induced β-catenin/tcf4 interaction original hdac7-binding protein beta-catenin signalling hdac7-mediated nsclc progression hdac7-meditated nsclc progression decreased acetylation levels hdac7-mediated nsclc proliferation study-related procedures began privacy choices/manage cookies fgf18-overexpressing cells presented β-catenin pathway sharing hdac7-mediated posttranslational modification background worldwide hdac7-enhanced migratory abilities hdac7-regulated nsclc progression kaplan–meier method received respective treatments bmc β-catenin signaling

Schema {šŸ—ŗļø}

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         headline:HDAC7 promotes NSCLC proliferation and metastasis via stabilization by deubiquitinase USP10 and activation of β-catenin-FGF18 pathway
         description:Histone deacetylases (HDACs) play crucial roles in cancers, but the role and mechanism of HDAC7 in NSCLC have not been fully understood. A total of 319 patients with non-small cell lung cancer (NSCLC) who underwent surgery were enrolled in this study. Immunohistochemistry and Kaplan–Meier survival analysis were performed to investigate the relationship between HDAC7, fibroblast growth factor 18 (FGF18) expression, and clinicopathologic characteristics. Cell functional experiments were implemented both in vivo and in vitro to investigate the effects on NSCLC cell proliferation and metastasis. Recombinant lentivirus–meditated in vivo gene overexpression or knockdown, real-time polymerase chain reaction (PCR), western blotting, and coimmunoprecipitation assays were applied to clarify the underlying molecular mechanism of HDAC7 in promoting NSCLC progression. The elevated expression of HDAC7 or FGF18 was positively correlated with poor prognosis, tumor–node–metastasis (TNM) stage, and tumor differentiation of NSCLC patients. NSCLC patients with co-expressed HDAC7 and FGF18 suffered the worst prognosis. HDAC7 overexpression promoted NSCLC proliferation and metastasis by upregulating FGF18. Conversely, overexpression of FGF18 reversed the attenuated ability in tumor growth and metastasis mediated by downregulating HDAC7. In terms of mechanism, our results suggested that the interaction of HDAC7 with β-catenin caused decreased β-catenin acetylation level at Lys49 and decreased phosphorylation level at Ser45. As a consequence, the HDAC7-mediated posttranslational modification of β-catenin facilitated nuclear transfer and activated FGF18 expression via binding to TCF4. Furthermore, deubiquitinase USP10 interacted with and stabilized HDAC7. The suppression of USP10 significantly accelerated the degradation of HDAC7 and weakened NSCLC growth and migration. Our findings reveal that HDAC7 promotes NSCLC progression through being stabilized by USP10 and activating the β-catenin-FGF18 pathway. Targeting this novel pathway may be a promising strategy for further developments in NSCLC therapy.
         datePublished:2022-03-11T00:00:00Z
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      headline:HDAC7 promotes NSCLC proliferation and metastasis via stabilization by deubiquitinase USP10 and activation of β-catenin-FGF18 pathway
      description:Histone deacetylases (HDACs) play crucial roles in cancers, but the role and mechanism of HDAC7 in NSCLC have not been fully understood. A total of 319 patients with non-small cell lung cancer (NSCLC) who underwent surgery were enrolled in this study. Immunohistochemistry and Kaplan–Meier survival analysis were performed to investigate the relationship between HDAC7, fibroblast growth factor 18 (FGF18) expression, and clinicopathologic characteristics. Cell functional experiments were implemented both in vivo and in vitro to investigate the effects on NSCLC cell proliferation and metastasis. Recombinant lentivirus–meditated in vivo gene overexpression or knockdown, real-time polymerase chain reaction (PCR), western blotting, and coimmunoprecipitation assays were applied to clarify the underlying molecular mechanism of HDAC7 in promoting NSCLC progression. The elevated expression of HDAC7 or FGF18 was positively correlated with poor prognosis, tumor–node–metastasis (TNM) stage, and tumor differentiation of NSCLC patients. NSCLC patients with co-expressed HDAC7 and FGF18 suffered the worst prognosis. HDAC7 overexpression promoted NSCLC proliferation and metastasis by upregulating FGF18. Conversely, overexpression of FGF18 reversed the attenuated ability in tumor growth and metastasis mediated by downregulating HDAC7. In terms of mechanism, our results suggested that the interaction of HDAC7 with β-catenin caused decreased β-catenin acetylation level at Lys49 and decreased phosphorylation level at Ser45. As a consequence, the HDAC7-mediated posttranslational modification of β-catenin facilitated nuclear transfer and activated FGF18 expression via binding to TCF4. Furthermore, deubiquitinase USP10 interacted with and stabilized HDAC7. The suppression of USP10 significantly accelerated the degradation of HDAC7 and weakened NSCLC growth and migration. Our findings reveal that HDAC7 promotes NSCLC progression through being stabilized by USP10 and activating the β-catenin-FGF18 pathway. Targeting this novel pathway may be a promising strategy for further developments in NSCLC therapy.
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      dateModified:2022-03-11T00:00:00Z
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      keywords:
         NSCLC
         HDAC7
         FGF18
         Ī²-catenin
         USP10
         Cancer Research
         Immunology
         Apoptosis
         Oncology
      image:
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                     type:PostalAddress
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      name:Air Force Medical University
      address:
         name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
         type:PostalAddress
      name:Air Force Medical University
      address:
         name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
         type:PostalAddress
      name:Tangdu Hospital, Air Force Medical University
      address:
         name:Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, China
         type:PostalAddress
      name:The Sixth Medical Center of PLA General Hospital
      address:
         name:Department of Thoracic Surgery, The Sixth Medical Center of PLA General Hospital, Beijing, China
         type:PostalAddress
      name:Air Force Medical University
      address:
         name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
         type:PostalAddress
      name:Air Force Medical University
      address:
         name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
         type:PostalAddress
      name:University of Turin, San Luigi Hospital
      address:
         name:Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Italy
         type:PostalAddress
      name:Karolinska University Hospital, Karolinska Institutet
      address:
         name:Thoracic Oncology Center, Department of Oncology-Pathology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
         type:PostalAddress
      name:Kindai University Faculty of Medicine
      address:
         name:Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
         type:PostalAddress
      name:Istituto Nazionale Tumori IRCCS ā€œRegina Elenaā€
      address:
         name:Istituto Nazionale Tumori IRCCS ā€œRegina Elenaā€, Roma, Italy
         type:PostalAddress
      name:Tangdu Hospital, Air Force Medical University
      address:
         name:Department of Ophthalmology, Tangdu Hospital, Air Force Medical University, Xi’an, China
         type:PostalAddress
      name:Air Force Medical University
      address:
         name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
         type:PostalAddress
      name:Air Force Medical University
      address:
         name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
         type:PostalAddress
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      name:Kai Guo
      affiliation:
            name:The Third Affiliated Hospital of Xi’an Jiaotong University
            address:
               name:Department of Thoracic Surgery, Shaanxi Provincial People’s Hospital, The Third Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
               type:PostalAddress
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            name:Air Force Medical University
            address:
               name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
               type:PostalAddress
            type:Organization
      name:Zhiqiang Ma
      affiliation:
            name:The Fifth Medical Center of PLA General Hospital
            address:
               name:Department of Medical Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China
               type:PostalAddress
            type:Organization
      name:Yujiao Zhang
      affiliation:
            name:the Second Affiliated Hospital of Xi’an Jiaotong University
            address:
               name:Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
               type:PostalAddress
            type:Organization
      name:Lu Han
      affiliation:
            name:Xi’an Central Hospital, Xi’an Jiaotong University
            address:
               name:Department of Ultrasound, Xi’an Central Hospital, Xi’an Jiaotong University, Xi’an, China
               type:PostalAddress
            type:Organization
      name:Changjian Shao
      affiliation:
            name:Air Force Medical University
            address:
               name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
               type:PostalAddress
            type:Organization
      name:Yingtong Feng
      affiliation:
            name:Air Force Medical University
            address:
               name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
               type:PostalAddress
            type:Organization
      name:Fei Gao
      affiliation:
            name:Tangdu Hospital, Air Force Medical University
            address:
               name:Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, China
               type:PostalAddress
            type:Organization
      name:Shouyin Di
      affiliation:
            name:The Sixth Medical Center of PLA General Hospital
            address:
               name:Department of Thoracic Surgery, The Sixth Medical Center of PLA General Hospital, Beijing, China
               type:PostalAddress
            type:Organization
      name:Zhipei Zhang
      affiliation:
            name:Air Force Medical University
            address:
               name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
               type:PostalAddress
            type:Organization
      name:Jiao Zhang
      affiliation:
            name:Air Force Medical University
            address:
               name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
               type:PostalAddress
            type:Organization
      name:Fabrizio Tabbò
      affiliation:
            name:University of Turin, San Luigi Hospital
            address:
               name:Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Italy
               type:PostalAddress
            type:Organization
      name:Simon Ekman
      affiliation:
            name:Karolinska University Hospital, Karolinska Institutet
            address:
               name:Thoracic Oncology Center, Department of Oncology-Pathology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
               type:PostalAddress
            type:Organization
      name:Kenichi Suda
      affiliation:
            name:Kindai University Faculty of Medicine
            address:
               name:Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
               type:PostalAddress
            type:Organization
      name:Federico Cappuzzo
      affiliation:
            name:Istituto Nazionale Tumori IRCCS ā€œRegina Elenaā€
            address:
               name:Istituto Nazionale Tumori IRCCS ā€œRegina Elenaā€, Roma, Italy
               type:PostalAddress
            type:Organization
      name:Jing Han
      affiliation:
            name:Tangdu Hospital, Air Force Medical University
            address:
               name:Department of Ophthalmology, Tangdu Hospital, Air Force Medical University, Xi’an, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Xiaofei Li
      affiliation:
            name:Air Force Medical University
            address:
               name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Xiaolong Yan
      url:http://orcid.org/0000-0003-2419-9707
      affiliation:
            name:Air Force Medical University
            address:
               name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Thoracic Surgery, Shaanxi Provincial People’s Hospital, The Third Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
      name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
      name:Department of Medical Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China
      name:Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
      name:Department of Ultrasound, Xi’an Central Hospital, Xi’an Jiaotong University, Xi’an, China
      name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
      name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
      name:Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, China
      name:Department of Thoracic Surgery, The Sixth Medical Center of PLA General Hospital, Beijing, China
      name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
      name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
      name:Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Italy
      name:Thoracic Oncology Center, Department of Oncology-Pathology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
      name:Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
      name:Istituto Nazionale Tumori IRCCS ā€œRegina Elenaā€, Roma, Italy
      name:Department of Ophthalmology, Tangdu Hospital, Air Force Medical University, Xi’an, China
      name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China
      name:Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi’an , China

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