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

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-05-08 DOI:10.1016/j.tranon.2025.102404

Pincheng Zhou , Fengze Sun , Peixu Lin , Yan Yan , Jiayao Liu , Yang Zhou , Ting He , Pengcheng Liu , Jie Wang , Huanhuan Sun , Haiqing Ma

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引用次数: 0

Abstract

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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雌激素抑制依赖于HOXA11- as /HOXA11的肝细胞癌进展

雌激素在肝癌细胞中的作用已引起人们的关注，但其具体作用和潜在机制尚不清楚。方法采用流式细胞术和Western blotting检测HOXA11-AS和雌激素促进肝癌细胞凋亡的作用机制。体内皮下肿瘤发生试验证实了HOXA11-AS在HCC进展中的调节作用。通过免疫组化，探讨HOXA11表达与HCC患者预后的关系。结果研究发现，雌激素可促进HCC细胞凋亡，其作用依赖于HOXA11-AS。HOXA11和HOXA11- as在HCC组织中表达上调。下调HOXA11- as和HOXA11可显著抑制HCC中细胞的增殖、迁移和侵袭。HOXA11- as与HOXA11形成RNA双工，阻止RNase降解。在HCC患者中，高HOXA11表达与较低的总生存期（OS）（p=0.001）和无病生存期（DFS）（p=0.002）显著相关。高表达的HOXA11也与复发（p<0.001）、大血管侵犯（p=0.002）和肿瘤体积增加（p=0.007）显著相关。雌激素激活HCC细胞系中c-met/AKT/mTOR通路。结论雌激素及其相关蛋白对肝癌有治疗作用，可能是新的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the 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 oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.