AP5Z1 affects hepatocellular carcinoma growth and autophagy by regulating PTEN ubiquitination and modulating the PI3K/Akt/mTOR pathway
Abstract Background Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, with high incidence and mortality rates, and the number of cases is expected to increase by 2030. Understanding the molecular mechanisms of HCC and identifying new therapeutic targets and biomarkers for...
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BMC
2025-05-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06537-9 |
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| author | Zhipeng Quan Bo Peng Kai Hu Lixing Liang Mingjiang Liu Lijuan Liao Shilian Chen Jing Qin Songqing He Zeyuan Li |
| author_facet | Zhipeng Quan Bo Peng Kai Hu Lixing Liang Mingjiang Liu Lijuan Liao Shilian Chen Jing Qin Songqing He Zeyuan Li |
| author_sort | Zhipeng Quan |
| collection | DOAJ |
| description | Abstract Background Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, with high incidence and mortality rates, and the number of cases is expected to increase by 2030. Understanding the molecular mechanisms of HCC and identifying new therapeutic targets and biomarkers for HCC are crucial. Methods In this study, we examined adaptor-related protein complex 5 subunit ζ1 (AP5Z1) expression in liver cancer and nearby noncancerous tissues to explore its effects on HCC cell growth, death, and autophagy. The functional and molecular mechanisms of AP5Z1 were studied using clinical sample analysis, Western blot (WB), immunohistochemistry (IHC), quantitative reverse-transcription polymerase chain reaction (qRT‒PCR), coimmunoprecipitation (Co-IP), cell proliferation assays, flow cytometry (FCM), autophagy assays, electron microscopy, mass spectrometry (MS), transcriptome analysis, and animal model experiments. Results AP5Z1 expression was notably higher in HCC tissues than in normal tissues and was linked to a poor prognosis. The results of both in vitro and in vivo studies revealed that AP5Z1 promoted HCC cell growth and reduced apoptosis. In addition, AP5Z1 regulates cellular autophagy by ubiquitinating the phosphatase and tensin homolog (PTEN) protein and modulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Conclusions AP5Z1 influences autophagy and apoptosis in HCC cells by interacting with PTEN to modulate the PI3K/Akt/mTOR pathway. This gene might promote PTEN ubiquitination and degradation by recruiting tripartite motif-containing protein 21 (TRIM21), making it a potential biomarker for diagnosing and predicting the outcome of HCC as well as a target for new treatment strategies. |
| format | Article |
| id | doaj-art-36b030e63cf14d07af0bd143111de591 |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-36b030e63cf14d07af0bd143111de5912025-08-20T01:53:19ZengBMCJournal of Translational Medicine1479-58762025-05-0123111810.1186/s12967-025-06537-9AP5Z1 affects hepatocellular carcinoma growth and autophagy by regulating PTEN ubiquitination and modulating the PI3K/Akt/mTOR pathwayZhipeng Quan0Bo Peng1Kai Hu2Lixing Liang3Mingjiang Liu4Lijuan Liao5Shilian Chen6Jing Qin7Songqing He8Zeyuan Li9Division of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical UniversityGuangxi Key Laboratory of Immunology and Metabolism for Liver DiseasesGuangxi Key Laboratory of Immunology and Metabolism for Liver DiseasesDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical UniversityGuangxi Key Laboratory of Immunology and Metabolism for Liver DiseasesDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical UniversityAbstract Background Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, with high incidence and mortality rates, and the number of cases is expected to increase by 2030. Understanding the molecular mechanisms of HCC and identifying new therapeutic targets and biomarkers for HCC are crucial. Methods In this study, we examined adaptor-related protein complex 5 subunit ζ1 (AP5Z1) expression in liver cancer and nearby noncancerous tissues to explore its effects on HCC cell growth, death, and autophagy. The functional and molecular mechanisms of AP5Z1 were studied using clinical sample analysis, Western blot (WB), immunohistochemistry (IHC), quantitative reverse-transcription polymerase chain reaction (qRT‒PCR), coimmunoprecipitation (Co-IP), cell proliferation assays, flow cytometry (FCM), autophagy assays, electron microscopy, mass spectrometry (MS), transcriptome analysis, and animal model experiments. Results AP5Z1 expression was notably higher in HCC tissues than in normal tissues and was linked to a poor prognosis. The results of both in vitro and in vivo studies revealed that AP5Z1 promoted HCC cell growth and reduced apoptosis. In addition, AP5Z1 regulates cellular autophagy by ubiquitinating the phosphatase and tensin homolog (PTEN) protein and modulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Conclusions AP5Z1 influences autophagy and apoptosis in HCC cells by interacting with PTEN to modulate the PI3K/Akt/mTOR pathway. This gene might promote PTEN ubiquitination and degradation by recruiting tripartite motif-containing protein 21 (TRIM21), making it a potential biomarker for diagnosing and predicting the outcome of HCC as well as a target for new treatment strategies.https://doi.org/10.1186/s12967-025-06537-9Hepatocellular carcinomaAP5Z1PTENTRIM21AutophagyApoptosis |
| spellingShingle | Zhipeng Quan Bo Peng Kai Hu Lixing Liang Mingjiang Liu Lijuan Liao Shilian Chen Jing Qin Songqing He Zeyuan Li AP5Z1 affects hepatocellular carcinoma growth and autophagy by regulating PTEN ubiquitination and modulating the PI3K/Akt/mTOR pathway Journal of Translational Medicine Hepatocellular carcinoma AP5Z1 PTEN TRIM21 Autophagy Apoptosis |
| title | AP5Z1 affects hepatocellular carcinoma growth and autophagy by regulating PTEN ubiquitination and modulating the PI3K/Akt/mTOR pathway |
| title_full | AP5Z1 affects hepatocellular carcinoma growth and autophagy by regulating PTEN ubiquitination and modulating the PI3K/Akt/mTOR pathway |
| title_fullStr | AP5Z1 affects hepatocellular carcinoma growth and autophagy by regulating PTEN ubiquitination and modulating the PI3K/Akt/mTOR pathway |
| title_full_unstemmed | AP5Z1 affects hepatocellular carcinoma growth and autophagy by regulating PTEN ubiquitination and modulating the PI3K/Akt/mTOR pathway |
| title_short | AP5Z1 affects hepatocellular carcinoma growth and autophagy by regulating PTEN ubiquitination and modulating the PI3K/Akt/mTOR pathway |
| title_sort | ap5z1 affects hepatocellular carcinoma growth and autophagy by regulating pten ubiquitination and modulating the pi3k akt mtor pathway |
| topic | Hepatocellular carcinoma AP5Z1 PTEN TRIM21 Autophagy Apoptosis |
| url | https://doi.org/10.1186/s12967-025-06537-9 |
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