2. Academic Validation
  3. HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway

HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway

  • Cell Death Dis. 2023 Sep 14;14(9):606. doi: 10.1038/s41419-023-06076-5.
Tao Han # 1,  Tingsong Chen # 2,  Lujun Chen # 1 3,  Kerui Li 1,  Daimin Xiang 4 5,  Lei Dou 6,  Hengyu Li 7,  Yubei Gu 8
Affiliations

Affiliations

  • 1 Department of Oncology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
  • 2 Department of Cancer Intervention, Seventh People's Hospital of Shanghai University of TCM, Shanghai, 200001, China.
  • 3 Postgraduate College, China Medical University, Shenyang, 110001, China.
  • 4 Clinical Cancer Institute, Center for Translational Medicine, Naval Military Medical University, Shanghai, 200433, China.
  • 5 Department of hepatobiliary surgery, East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
  • 6 Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China. [email protected].
  • 7 Department of Breast and Thyroid Surgery, Changhai Hospital, Naval Military Medical University, Shanghai, 200433, China. [email protected].
  • 8 Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 37709768 DOI: 10.1038/s41419-023-06076-5
Abstract

Hepatic leukemia factor (HLF) is aberrantly expressed in human malignancies. However, the role of HLF in the regulation of ovarian Cancer (OC) remains unknown. Herein, we reported that HLF expression was upregulated in OC tissues and ovarian Cancer Stem Cells (CSCs). Functional studies have revealed that HLF regulates OC cell stemness, proliferation, and metastasis. Mechanistically, HLF transcriptionally activated Yes-associated protein 1 (YAP1) expression and subsequently modulated the Hippo signaling pathway. Moreover, we found that miR-520e directly targeted HLF 3'-UTR in OC cells. miR-520e expression was negatively correlated with HLF and YAP1 expression in OC tissues. The combined immunohistochemical (IHC) panels exhibited a better prognostic value for OC patients than any of these components alone. Importantly, the HLF/YAP1 axis determines the response of OC cells to carboplatin treatment and HLF depletion or the YAP1 inhibitor verteporfin abrogated carboplatin resistance. Analysis of patient-derived xenografts (PDXs) further suggested that HLF might predict carboplatin benefits in OC patients. In conclusion, these findings suggest a crucial role of the miR-520e/HLF/YAP1 axis in OC progression and chemoresistance, suggesting potential therapeutic targets for OC.

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