School of Medicine, Jinan University, Guangzhou, China.
International Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen, China.
J Cell Mol Med. 2024 Oct;28(20):e70120. doi: 10.1111/jcmm.70120.
Ovarian cancer is of the most lethal malignancy and causes serious threat to women health worldwide. A deep understanding of molecular mechanisms underlying ovarian cancer progression is critical for the development of promising therapeutic strategies. In this study, we aimed to employ immunohistochemistry to determine the protein level of HDAC7 in patient tissues, our data showed HDAC7 levels are upregulated in tumour tissues. In addition, we also performed Kaplan-Meier survival analysis to investigate the association between HDAC7 expression and clinical prognosis, and found that HDAC7 expression was associated with poor prognosis in ovarian cancer patients. Inhibition of HDAC7 cells resulted in lower cell proliferation, invasion and colony formation. Furthermore, we also found that HDAC7 inhibition suppressed PI3K/AKT/mTOR pathway. In contrast, exogenous HDAC7 expression activated the PI3K/AKT/mTOR pathway in HDAC7 knockout cells and rescued the cell proliferation, invasion and colony formation. However, inhibition of p-AKT induced lower cell proliferation, metastasis and colony formation abilities. In murine model, HDAC7 KO significantly decreased the tumour burden. These data indicate that HDAC7 is involved in regulation of PI3K/AKT/mTOR pathway and targeting of HDAC7 could be potential therapeutic strategy in the treatment of ovarian cancer.
卵巢癌是最致命的恶性肿瘤之一，对全球女性健康造成严重威胁。深入了解卵巢癌进展的分子机制对于开发有前途的治疗策略至关重要。在这项研究中，我们旨在通过免疫组织化学来确定患者组织中 HDAC7 的蛋白水平，我们的数据显示 HDAC7 水平在肿瘤组织中上调。此外，我们还进行了 Kaplan-Meier 生存分析，以研究 HDAC7 表达与临床预后之间的关系，发现 HDAC7 表达与卵巢癌患者的不良预后相关。抑制 HDAC7 细胞导致细胞增殖、侵袭和集落形成能力降低。此外，我们还发现 HDAC7 抑制抑制了 PI3K/AKT/mTOR 通路。相比之下，外源性 HDAC7 表达在 HDAC7 敲除细胞中激活了 PI3K/AKT/mTOR 通路，并挽救了细胞增殖、侵袭和集落形成能力。然而，抑制 p-AKT 诱导的细胞增殖、转移和集落形成能力降低。在小鼠模型中，HDAC7 KO 显著降低了肿瘤负担。这些数据表明，HDAC7 参与调节 PI3K/AKT/mTOR 通路，靶向 HDAC7 可能是治疗卵巢癌的潜在治疗策略。
