{"title":"GLYAT suppresses liver cancer and clear cell renal cell carcinoma progression by downregulating ROCK1 expression.","authors":"Yechen Xia, Wentao Huang, Guang-Zhi Jin","doi":"10.21037/tcr-24-1412","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The liver and kidney are important metabolic organs in the body and common sites of tumor occurrence. Glycine-N-acyltransferase (GLYAT) is primarily expressed in the liver and kidney and downregulated in several tumors. But its specific functions and molecular mechanisms in liver cancer and clear cell renal cell carcinoma (ccRCC) have not yet been fully elucidated. The aim of this study was to explore the role and clinical significance of GLYAT in liver cancer and ccRCC.</p><p><strong>Methods: </strong>This study used proteomics technology to identify differentially expressed proteins in liver cancer. Western blot and immunohistochemistry (IHC) were used to analyze the protein expression pattern of GLYAT. assays were performed in liver cancer and ccRCC cells. Xenograft models in nude mice were used to confirm the roles of GLYAT in liver cancer. Moreover, the downstream regulatory proteins of GLYAT were identified by proteomics.</p><p><strong>Results: </strong>GLYAT was lowly expressed in liver cancer and ccRCC. Immunofluorescence staining indicated that GLYAT was mainly expressed in the cytoplasm, particularly the mitochondria. Kaplan-Meier curves showed that the low protein expression of GLYAT was correlated with a poor prognosis in liver cancer and ccRCC patients. Moreover, GLYAT expression was associated with several clinical parameters in liver cancer. Cell experiments showed that the overexpression of GLYAT inhibited cell proliferation and migration abilities; however, interfering GLYAT protein expression rescued these abilities in GLYAT overexpression (GLYAT-OE) cells. <i>In vivo</i> assays confirmed the tumor-suppressor function of GLYAT in liver cancer. Moreover, our research showed that GLYAT downregulated Rho-associated coiled-coil-containing protein kinase 1 (ROCK1).</p><p><strong>Conclusions: </strong>Our study showed that GLYAT is lowly expressed in liver cancer and ccRCC, emphasizing its prognostic significance. It also showed that GLYAT inhibits the progression of liver cancer and ccRCC by downregulating ROCK1.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 9","pages":"5097-5111"},"PeriodicalIF":1.5000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483444/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-24-1412","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/27 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The liver and kidney are important metabolic organs in the body and common sites of tumor occurrence. Glycine-N-acyltransferase (GLYAT) is primarily expressed in the liver and kidney and downregulated in several tumors. But its specific functions and molecular mechanisms in liver cancer and clear cell renal cell carcinoma (ccRCC) have not yet been fully elucidated. The aim of this study was to explore the role and clinical significance of GLYAT in liver cancer and ccRCC.
Methods: This study used proteomics technology to identify differentially expressed proteins in liver cancer. Western blot and immunohistochemistry (IHC) were used to analyze the protein expression pattern of GLYAT. assays were performed in liver cancer and ccRCC cells. Xenograft models in nude mice were used to confirm the roles of GLYAT in liver cancer. Moreover, the downstream regulatory proteins of GLYAT were identified by proteomics.
Results: GLYAT was lowly expressed in liver cancer and ccRCC. Immunofluorescence staining indicated that GLYAT was mainly expressed in the cytoplasm, particularly the mitochondria. Kaplan-Meier curves showed that the low protein expression of GLYAT was correlated with a poor prognosis in liver cancer and ccRCC patients. Moreover, GLYAT expression was associated with several clinical parameters in liver cancer. Cell experiments showed that the overexpression of GLYAT inhibited cell proliferation and migration abilities; however, interfering GLYAT protein expression rescued these abilities in GLYAT overexpression (GLYAT-OE) cells. In vivo assays confirmed the tumor-suppressor function of GLYAT in liver cancer. Moreover, our research showed that GLYAT downregulated Rho-associated coiled-coil-containing protein kinase 1 (ROCK1).
Conclusions: Our study showed that GLYAT is lowly expressed in liver cancer and ccRCC, emphasizing its prognostic significance. It also showed that GLYAT inhibits the progression of liver cancer and ccRCC by downregulating ROCK1.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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