HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway.
HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway.
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HLF通过调节Hippo信号通路促进卵巢癌的进展和化疗耐药。
DOI：
10.1038/s41419-023-06076-5
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发表时间：
2023-09-14
影响因子：
9
通讯作者：
Gu Y
中科院分区：
文献类型：
--
作者：
Han T;Chen T;Chen L;Li K;Xiang D;Dou L;Li H;Gu Y
肝白血病因子（HLF）在人类恶性肿瘤中异常表达。然而，HLF在卵巢癌（OC）的调节中的作用仍然未知。在此，我们报道了HLF在OC组织和卵巢癌干细胞（CSC）中的表达上调。功能研究表明，HLF调节OC细胞的干细胞性、增殖和转移。机制上，HLF转录激活的是相关蛋白1（YAP 1）的表达，并随后调制海马信号通路。此外，我们还发现miR-520 e直接靶向OC细胞中的HLF 3′-UTR。OC组织中miR-520 e的表达与HLF和YAP 1的表达呈负相关。联合免疫组化（IHC）面板表现出更好的预后价值OC患者比任何这些组件单独。重要的是，HLF/YAP 1轴决定OC细胞对卡铂治疗和HLF消耗或YAP 1抑制剂维替泊芬消除卡铂抗性的反应。对患者来源的异种移植物（PDX）的分析进一步表明，HLF可能预测卡铂在OC患者中的获益。总之，这些发现表明miR-520 e/HLF/YAP 1轴在OC进展和化疗耐药性中起着至关重要的作用，提示了OC的潜在治疗靶点。
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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影响因子：
8
作者：
He C;Lv X;Hua G;Lele SM;Remmenga S;Dong J;Davis JS;Wang C
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29.4
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