雌激素通过依赖HOXA11-AS/HOXA11抑制肝细胞癌进展。

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

作者信息

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

机构信息

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.

Zhuhai 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, China.

出版信息

Transl Oncol. 2025 Jul;57:102404. doi: 10.1016/j.tranon.2025.102404. Epub 2025 May 8.

DOI:10.1016/j.tranon.2025.102404

PMID:40344916

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12138468/

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.

摘要

背景

雌激素在肝癌细胞中的作用已引起关注，但其具体作用及潜在机制仍不清楚。

方法

采用流式细胞术和蛋白质免疫印迹法研究HOXA11-AS和雌激素促进肝细胞癌（HCC）凋亡的机制。通过体内皮下成瘤实验证实HOXA11-AS在HCC进展中的调控作用。通过免疫组化探讨HOXA11表达与HCC患者预后的相关性。

结果

发现雌激素依赖HOXA11-AS促进HCC细胞凋亡。HOXA11和HOXA11-AS在HCC组织中上调。下调HOXA11-AS和HOXA11可显著抑制HCC细胞的增殖、迁移和侵袭。HOXA11-AS与HOXA11形成RNA双链体，防止核糖核酸酶降解。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HOXA11表达还与复发（p<0.001）、主要血管侵犯（p=0.002）和肿瘤体积增大（p=0.007）显著相关。雌激素激活了HCC细胞系中的c-met/AKT/mTOR信号通路。