STOX1 Isoform A Promotes Proliferation and Progression of Hepatocellular Carcinoma by Dual Mechanisms of Transcriptionally Upregulation of Cyclin B1 and Activation of ROS‐Dependent PTEN/AKT1 Signaling
ABSTRACT Background Dysregulation of transcription factors is one of the most common factors for the pathogenesis of hepatocellular carcinoma (HCC). To the best of our knowledge, no study has yet investigated the clinical significance and functional role of STOX1 in HCC. Methods Real‐time PCR, Weste...
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2025-07-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70958 |
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| author | Chunlin Jiang Chong Wang Jian Ao Yangping Liu Fengjie Sun Wangpan Shi Zeyi Guo Yanping Wu Luxiang Gan Meimei Wu Yaofeng Zhi Zijie Meng Wanting Wu Juanhua Wu Yong Ye Xin Zhang Dong Ren Mingxin Pan |
| author_facet | Chunlin Jiang Chong Wang Jian Ao Yangping Liu Fengjie Sun Wangpan Shi Zeyi Guo Yanping Wu Luxiang Gan Meimei Wu Yaofeng Zhi Zijie Meng Wanting Wu Juanhua Wu Yong Ye Xin Zhang Dong Ren Mingxin Pan |
| author_sort | Chunlin Jiang |
| collection | DOAJ |
| description | ABSTRACT Background Dysregulation of transcription factors is one of the most common factors for the pathogenesis of hepatocellular carcinoma (HCC). To the best of our knowledge, no study has yet investigated the clinical significance and functional role of STOX1 in HCC. Methods Real‐time PCR, Western blotting and immunohistochemistry were performed to examine the expression of STOX1‐A in HCC specimens. Animal experiment in vivo and functional cell assays in vitro were used to investigate the tumorigenic and proliferative ability of HCC cells. Luciferase and ROS assays were depolyed to investigate the molecular mechanisms underlying the biologic role of STOX1‐A in HCC. Results In this study, we report that STOX1 isoform A (STOX1‐A) is significantly upregulated in HCC tissues, and elevated STOX1‐A levels are associated with poorer overall survival and progression‐free survival in HCC patients. Functional assays demonstrated that STOX1‐A upregulation promotes, whereas its silencing suppresses, HCC cell proliferation and growth both in vitro and in vivo. Mechanistic investigations revealed a dual mechanism by which STOX1‐A drives HCC progression. First, STOX1‐A transcriptionally upregulates cyclin B1, promoting cell proliferation. Second, it activates the AKT1 signaling pathway through reactive oxygen species (ROS)‐mediated deactivation of PTEN. Furthermore, a positive correlation between STOX1‐A expression and the levels of cyclin B1 and phosphorylated AKT1 (p‐AKT1 Ser473) was observed in clinical HCC samples. Conclusion Our findings identify a novel dual mechanism by which STOX1‐A promotes HCC proliferation and growth, offering potential avenues for the development of anti‐tumor therapeutic strategies targeting STOX1‐A in HCC. |
| format | Article |
| id | doaj-art-5068c5af587c4190b4bc9a7fa96b7dad |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-5068c5af587c4190b4bc9a7fa96b7dad2025-08-20T03:34:09ZengWileyCancer Medicine2045-76342025-07-011413n/an/a10.1002/cam4.70958STOX1 Isoform A Promotes Proliferation and Progression of Hepatocellular Carcinoma by Dual Mechanisms of Transcriptionally Upregulation of Cyclin B1 and Activation of ROS‐Dependent PTEN/AKT1 SignalingChunlin Jiang0Chong Wang1Jian Ao2Yangping Liu3Fengjie Sun4Wangpan Shi5Zeyi Guo6Yanping Wu7Luxiang Gan8Meimei Wu9Yaofeng Zhi10Zijie Meng11Wanting Wu12Juanhua Wu13Yong Ye14Xin Zhang15Dong Ren16Mingxin Pan17Department of Hepatobiliary Surgery II, Zhujiang Hospital Southern Medical University Guangzhou P. R. ChinaGeneral Surgery The Fifth Affiliated Hospital of Guangzhou Medical University Guangzhou P. R. ChinaGeneral Surgery The Fifth Affiliated Hospital of Guangzhou Medical University Guangzhou P. R. ChinaLogistics Department The First Affiliated Hospital of Sun Yat‐sen University Guangzhou P. R. ChinaKey Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes Guangzhou P. R. ChinaDepartment of Pathology University of California San Diego Health System San Diego California USADepartment of Hepatobiliary Surgery II, Zhujiang Hospital Southern Medical University Guangzhou P. R. ChinaDepartment of Hepatobiliary Surgery II, Zhujiang Hospital Southern Medical University Guangzhou P. R. ChinaDepartment of Hepatobiliary Surgery II, Zhujiang Hospital Southern Medical University Guangzhou P. R. ChinaJiangmen Key Laboratory of Clinical Biobank and Translational Research, Clinical Experimental Center Jiangmen Central Hospital Jiangmen ChinaJiangmen Key Laboratory of Clinical Biobank and Translational Research, Clinical Experimental Center Jiangmen Central Hospital Jiangmen ChinaJiangmen Key Laboratory of Clinical Biobank and Translational Research, Clinical Experimental Center Jiangmen Central Hospital Jiangmen ChinaJiangmen Key Laboratory of Clinical Biobank and Translational Research, Clinical Experimental Center Jiangmen Central Hospital Jiangmen ChinaDepartment of Hepatobiliary, Pancreatic and Splenic Surgery, Jiangmen Central Hospital Affiliated Jiangmen Hospital of Sun Yat‐Sen University Jiangmen ChinaDepartment of Hepatobiliary, Pancreatic and Splenic Surgery, Jiangmen Central Hospital Affiliated Jiangmen Hospital of Sun Yat‐Sen University Jiangmen ChinaJiangmen Key Laboratory of Clinical Biobank and Translational Research, Clinical Experimental Center Jiangmen Central Hospital Jiangmen ChinaDepartment of Pathology University of California Irvine Medical Center Orange California USADepartment of Hepatobiliary Surgery II, Zhujiang Hospital Southern Medical University Guangzhou P. R. ChinaABSTRACT Background Dysregulation of transcription factors is one of the most common factors for the pathogenesis of hepatocellular carcinoma (HCC). To the best of our knowledge, no study has yet investigated the clinical significance and functional role of STOX1 in HCC. Methods Real‐time PCR, Western blotting and immunohistochemistry were performed to examine the expression of STOX1‐A in HCC specimens. Animal experiment in vivo and functional cell assays in vitro were used to investigate the tumorigenic and proliferative ability of HCC cells. Luciferase and ROS assays were depolyed to investigate the molecular mechanisms underlying the biologic role of STOX1‐A in HCC. Results In this study, we report that STOX1 isoform A (STOX1‐A) is significantly upregulated in HCC tissues, and elevated STOX1‐A levels are associated with poorer overall survival and progression‐free survival in HCC patients. Functional assays demonstrated that STOX1‐A upregulation promotes, whereas its silencing suppresses, HCC cell proliferation and growth both in vitro and in vivo. Mechanistic investigations revealed a dual mechanism by which STOX1‐A drives HCC progression. First, STOX1‐A transcriptionally upregulates cyclin B1, promoting cell proliferation. Second, it activates the AKT1 signaling pathway through reactive oxygen species (ROS)‐mediated deactivation of PTEN. Furthermore, a positive correlation between STOX1‐A expression and the levels of cyclin B1 and phosphorylated AKT1 (p‐AKT1 Ser473) was observed in clinical HCC samples. Conclusion Our findings identify a novel dual mechanism by which STOX1‐A promotes HCC proliferation and growth, offering potential avenues for the development of anti‐tumor therapeutic strategies targeting STOX1‐A in HCC.https://doi.org/10.1002/cam4.70958AKT1 signaling pathwaycell proliferation and cell cyclehepatocellular carcinomareactive oxygen speciesSTOX1 isoform A |
| spellingShingle | Chunlin Jiang Chong Wang Jian Ao Yangping Liu Fengjie Sun Wangpan Shi Zeyi Guo Yanping Wu Luxiang Gan Meimei Wu Yaofeng Zhi Zijie Meng Wanting Wu Juanhua Wu Yong Ye Xin Zhang Dong Ren Mingxin Pan STOX1 Isoform A Promotes Proliferation and Progression of Hepatocellular Carcinoma by Dual Mechanisms of Transcriptionally Upregulation of Cyclin B1 and Activation of ROS‐Dependent PTEN/AKT1 Signaling Cancer Medicine AKT1 signaling pathway cell proliferation and cell cycle hepatocellular carcinoma reactive oxygen species STOX1 isoform A |
| title | STOX1 Isoform A Promotes Proliferation and Progression of Hepatocellular Carcinoma by Dual Mechanisms of Transcriptionally Upregulation of Cyclin B1 and Activation of ROS‐Dependent PTEN/AKT1 Signaling |
| title_full | STOX1 Isoform A Promotes Proliferation and Progression of Hepatocellular Carcinoma by Dual Mechanisms of Transcriptionally Upregulation of Cyclin B1 and Activation of ROS‐Dependent PTEN/AKT1 Signaling |
| title_fullStr | STOX1 Isoform A Promotes Proliferation and Progression of Hepatocellular Carcinoma by Dual Mechanisms of Transcriptionally Upregulation of Cyclin B1 and Activation of ROS‐Dependent PTEN/AKT1 Signaling |
| title_full_unstemmed | STOX1 Isoform A Promotes Proliferation and Progression of Hepatocellular Carcinoma by Dual Mechanisms of Transcriptionally Upregulation of Cyclin B1 and Activation of ROS‐Dependent PTEN/AKT1 Signaling |
| title_short | STOX1 Isoform A Promotes Proliferation and Progression of Hepatocellular Carcinoma by Dual Mechanisms of Transcriptionally Upregulation of Cyclin B1 and Activation of ROS‐Dependent PTEN/AKT1 Signaling |
| title_sort | stox1 isoform a promotes proliferation and progression of hepatocellular carcinoma by dual mechanisms of transcriptionally upregulation of cyclin b1 and activation of ros dependent pten akt1 signaling |
| topic | AKT1 signaling pathway cell proliferation and cell cycle hepatocellular carcinoma reactive oxygen species STOX1 isoform A |
| url | https://doi.org/10.1002/cam4.70958 |
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