Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11

Background: The role of estrogen in liver cancer cells has attracted attention, but its specific actions and underlying mechanisms remain unclear. Methods: Flow CytoMetry and Western blotting were used to investigate the mechanism of HOXA11-AS and estrogen in promoting apoptosis of hepatocellular ca...

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Main Authors: Pincheng Zhou, Fengze Sun, Peixu Lin, Yan Yan, Jiayao Liu, Yang Zhou, Ting He, Pengcheng Liu, Jie Wang, Huanhuan Sun, Haiqing Ma
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523325001354
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author Pincheng Zhou
Fengze Sun
Peixu Lin
Yan Yan
Jiayao Liu
Yang Zhou
Ting He
Pengcheng Liu
Jie Wang
Huanhuan Sun
Haiqing Ma
author_facet Pincheng Zhou
Fengze Sun
Peixu Lin
Yan Yan
Jiayao Liu
Yang Zhou
Ting He
Pengcheng Liu
Jie Wang
Huanhuan Sun
Haiqing Ma
author_sort Pincheng Zhou
collection DOAJ
description Background: The role of estrogen in liver cancer cells has attracted attention, but its specific actions and underlying mechanisms remain unclear. Methods: Flow CytoMetry and Western blotting were used to investigate the mechanism of HOXA11-AS and estrogen in promoting apoptosis of hepatocellular carcinoma (HCC). In vivo subcutaneous tumorigenesis assays were uesd to confirm the regulatory role of HOXA11-AS in HCC progression. Through immunohistochemistry, the correlation between HOXA11 expression and the prognosis of patients with HCC was explored. Results: Estrogen was found to promote apoptosis in HCC cells, dependent on HOXA11-AS. HOXA11 and HOXA11-AS are upregulated in HCC tissues. Downregulation of HOXA11-AS and HOXA11 significantly inhibited cell proliferation, migration, and invasion in HCC. HOXA11-AS forms an RNA duplex with HOXA11, preventing RNase degradation. In HCC patients, high HOXA11 expression was significantly associated with lower overall survival (OS) (p=0.001) and disease-free survival (DFS) (p=0.002). High HOXA11 expression was also significantly correlated with recurrence (p<0.001), major vascular invasion (p=0.002) and increased tumor volume (p=0.007). Estrogen activated the c-met/AKT/mTOR pathway in the HCC cell line. Conclusion: Estrogen and its related proteins have therapeutic effects in HCC and may be new potential therapeutic targets.
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spelling doaj-art-ed11e641e1424f1e95b81d51273005b02025-08-20T03:53:56ZengElsevierTranslational Oncology1936-52332025-07-015710240410.1016/j.tranon.2025.102404Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11Pincheng Zhou0Fengze Sun1Peixu Lin2Yan Yan3Jiayao Liu4Yang Zhou5Ting He6Pengcheng Liu7Jie Wang8Huanhuan Sun9Haiqing Ma10School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China; Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, ChinaZhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University),Zhuhai, Guangdong 519000, China; The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, ChinaGuangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, ChinaThe Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, ChinaSchool of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China; Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, ChinaSchool of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China; Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, ChinaGuangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, ChinaGuangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, ChinaGuangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, ChinaGuangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, China; Corresponding authors.School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China; Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, China; Heyuan Hospital of Guangdong Provincial People’s Hospital, Heyuan People’s Hospital, Heyuan, Guangdong 517000, China; Corresponding authors.Background: The role of estrogen in liver cancer cells has attracted attention, but its specific actions and underlying mechanisms remain unclear. Methods: Flow CytoMetry and Western blotting were used to investigate the mechanism of HOXA11-AS and estrogen in promoting apoptosis of hepatocellular carcinoma (HCC). In vivo subcutaneous tumorigenesis assays were uesd to confirm the regulatory role of HOXA11-AS in HCC progression. Through immunohistochemistry, the correlation between HOXA11 expression and the prognosis of patients with HCC was explored. Results: Estrogen was found to promote apoptosis in HCC cells, dependent on HOXA11-AS. HOXA11 and HOXA11-AS are upregulated in HCC tissues. Downregulation of HOXA11-AS and HOXA11 significantly inhibited cell proliferation, migration, and invasion in HCC. HOXA11-AS forms an RNA duplex with HOXA11, preventing RNase degradation. In HCC patients, high HOXA11 expression was significantly associated with lower overall survival (OS) (p=0.001) and disease-free survival (DFS) (p=0.002). High HOXA11 expression was also significantly correlated with recurrence (p<0.001), major vascular invasion (p=0.002) and increased tumor volume (p=0.007). Estrogen activated the c-met/AKT/mTOR pathway in the HCC cell line. Conclusion: Estrogen and its related proteins have therapeutic effects in HCC and may be new potential therapeutic targets.http://www.sciencedirect.com/science/article/pii/S1936523325001354EstrogenHOXA11HOXA11-ASHepatocellular carcinoma
spellingShingle Pincheng Zhou
Fengze Sun
Peixu Lin
Yan Yan
Jiayao Liu
Yang Zhou
Ting He
Pengcheng Liu
Jie Wang
Huanhuan Sun
Haiqing Ma
Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11
Translational Oncology
Estrogen
HOXA11
HOXA11-AS
Hepatocellular carcinoma
title Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11
title_full Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11
title_fullStr Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11
title_full_unstemmed Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11
title_short Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11
title_sort estrogen inhibits hepatocellular carcinoma progression dependent on hoxa11 as hoxa11
topic Estrogen
HOXA11
HOXA11-AS
Hepatocellular carcinoma
url http://www.sciencedirect.com/science/article/pii/S1936523325001354
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