The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China.
Reprod Sci. 2024 Jul;31(7):1868-1880. doi: 10.1007/s43032-024-01456-4. Epub 2024 Jan 23.
Ovarian cancer (OV) is a highly aggressive malignancy with poor prognosis due to recurrence and drug resistance. Therefore, it is imperative to investigate the key molecular mechanisms underlying OV progression in order to develop promising diagnostic and therapeutic interventions. Although the importance of hematological and neurological expressed 1 (HN1) protein in hemopoietic cell and neurological development has been well-established, its function in cancer, particularly in OV, remains uncertain. In this study, we compared the expression of HN1 in ovarian cancers and para-tumor tissues and predicted potential related signaling pathways through enrichment analysis. In order to confirm the role of HN1 in vitro and vivo, we carried out a variety of experiments including bioinformation analysis, colony formation, flow cytometry analysis, and subcutaneous tumor models. The results demonstrated that HN1 was upregulated in OV and was negatively associated with clinical prognosis. Moreover, we observed that HN1 enhances cell proliferation, migration, and drug resistance, while suppressing apoptosis in OV cells. Notably, we discovered that HN1 functions as a novel regulator of mTOR pathways. Our findings suggest that HN1-mediated mTOR regulation facilitates OV advancement and targeting HN1 could provide a promising therapeutic approach for clinical OV treatment.
卵巢癌(OV)是一种侵袭性很强的恶性肿瘤,由于复发和耐药性,预后较差。因此,研究卵巢癌进展的关键分子机制至关重要,以便开发有前途的诊断和治疗干预措施。尽管血液学和神经系统表达 1(HN1)蛋白在造血细胞和神经系统发育中的重要性已经得到充分证实,但它在癌症中的功能,特别是在 OV 中的功能仍不确定。在这项研究中,我们比较了卵巢癌和肿瘤旁组织中 HN1 的表达,并通过富集分析预测了潜在的相关信号通路。为了在体外和体内证实 HN1 的作用,我们进行了多种实验,包括生物信息分析、集落形成、流式细胞术分析和皮下肿瘤模型。结果表明,HN1 在 OV 中上调,与临床预后呈负相关。此外,我们观察到 HN1 增强了 OV 细胞的增殖、迁移和耐药性,同时抑制了细胞凋亡。值得注意的是,我们发现 HN1 作为 mTOR 途径的新型调节剂发挥作用。我们的研究结果表明,HN1 介导的 mTOR 调节促进了 OV 的进展,靶向 HN1 可能为卵巢癌的临床治疗提供一种有前途的治疗方法。