Hematological and Neurological Expressed 1 Promotes Tumor Progression Through mTOR Signaling in Ovarian Cancer.

IF 2.6 3区 医学 Q2 OBSTETRICS & GYNECOLOGY Reproductive Sciences Pub Date : 2024-07-01 Epub Date: 2024-01-23 DOI:10.1007/s43032-024-01456-4
Pin Li, Li-Heng Qian, Ying-Na Liao, Yan-Zhi Gai, Hong Pan, Long Han, Hui-Zhen Nie
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Abstract

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.

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血液和神经表达 1 通过 mTOR 信号促进卵巢癌的肿瘤进展
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,预后很差。因此,当务之急是研究卵巢癌进展的关键分子机制,以开发出有前景的诊断和治疗干预措施。虽然血液和神经表达 1(HN1)蛋白在造血细胞和神经系统发育中的重要性已得到证实,但其在癌症中,尤其是在 OV 中的功能仍不确定。在本研究中,我们比较了 HN1 在卵巢癌和肿瘤旁组织中的表达,并通过富集分析预测了潜在的相关信号通路。为了证实 HN1 在体外和体内的作用,我们进行了多种实验,包括生物信息分析、集落形成、流式细胞仪分析和皮下肿瘤模型。结果表明,HN1 在 OV 中上调,并与临床预后呈负相关。此外,我们还观察到 HN1 能增强 OV 细胞的增殖、迁移和耐药性,同时抑制细胞凋亡。值得注意的是,我们发现 HN1 是一种新型的 mTOR 通路调控因子。我们的研究结果表明,HN1 介导的 mTOR 调节促进了 OV 的发展,而靶向 HN1 可为临床 OV 治疗提供一种有前景的治疗方法。
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来源期刊
Reproductive Sciences
Reproductive Sciences 医学-妇产科学
CiteScore
5.50
自引率
3.40%
发文量
322
审稿时长
4-8 weeks
期刊介绍: Reproductive Sciences (RS) is a peer-reviewed, monthly journal publishing original research and reviews in obstetrics and gynecology. RS is multi-disciplinary and includes research in basic reproductive biology and medicine, maternal-fetal medicine, obstetrics, gynecology, reproductive endocrinology, urogynecology, fertility/infertility, embryology, gynecologic/reproductive oncology, developmental biology, stem cell research, molecular/cellular biology and other related fields.
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