2. Academic Validation
  3. Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11

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

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: sunhuanhuan@gdph.org.cn.
  • 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: mahaiqing@gdph.org.cn.
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.

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