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

  • Transl Oncol. 2025 Jul:57:102404. doi: 10.1016/j.tranon.2025.102404.
Pincheng Zhou  1 ,  Fengze Sun  2 ,  Peixu Lin  3 ,  Yan Yan  4 ,  Jiayao Liu  1 ,  Yang Zhou  1 ,  Ting He  3 ,  Pengcheng Liu  3 ,  Jie Wang  3 ,  Huanhuan Sun  5 ,  Haiqing Ma  6
Affiliations
  • 1. 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.
  • 2. 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.
  • 3. Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, China.
  • 4. The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China.
  • 5. Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University,Guangzhou, Guangdong 510006, China. Electronic address: [email protected].
  • 6. 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. Electronic address: [email protected].
PMID: 40344916 DOI: 10.1016/j.tranon.2025.102404
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.

Keywords
Estrogen; HOXA11; HOXA11-AS; Hepatocellular carcinoma.
Products