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NEK6作为一种癌基因,促进卵巢癌的增殖和转移。

NEK6 functions as an oncogene to promote the proliferation and metastasis of ovarian cancer.

作者信息

Gao Sainan, Su Min, Bian Tingting, Liu Yifei, Xu Yanhua, Zhang Yuquan

机构信息

Suzhou Medical College of Soochow University, Suzhou 215123, China.

Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, China.

出版信息

J Cancer. 2025 Jan 13;16(4):1335-1346. doi: 10.7150/jca.103769. eCollection 2025.

Abstract

Ovarian cancer (OC) is a common malignant tumor of the female reproductive organs. The novel serine/threonine kinase NEK6 is highly expressed in various cancers and affects the prognosis of patients. However, the role of NEK6 in OC is still unclear. In this study, the expression profiles of NEK6 in OC and its roles in the development of OC were investigated. The expression profiles of NEK6 across cancers and OC were explored using bioinformatics analysis, and its expression in OC patients was detected by immunohistochemical (IHC) staining. The correlation between its expression and clinicopathological factors was also analyzed. Furthermore, the NEK6 levels in the tumor tissues of OC patients were detected via RT‒qPCR and Western blotting. Biological functions, including cell growth, migration, invasion and apoptosis, were analyzed using MTT, Transwell and flow cytometry assays, respectively. Bioinformatics analysis revealed that NEK6 was highly expressed in most human cancers, including OC. IHC revealed 67.27% moderate or strong NEK6 staining in tumor tissues, 32.73% (36/110) weak staining, and negative or weak NEK6 staining in normal ovarian tissues, and its high expression was correlated with clinicopathological factors, including histological grade (=0.008) and metastasis (=0.006). The Kaplan‒Meier survival curve revealed that OC patients with high expression of NEK6 had poorer overall survival rates (=0.025). NEK6 was overexpressed in OC tissues and SK-OV-3 and A2780 cells, and when NEK6 was knocked down with siRNAs, cell growth, migration and invasion were inhibited, whereas cell apoptosis was significantly promoted. NEK6 is highly expressed in OC; its overexpression indicates poor prognosis; and NEK6 knockdown leads to inhibited growth, migration and invasion while promoting the apoptosis of OC cells. These findings indicate that NEK6 is a potential oncogene and a poor prognostic factor in OC, suggesting that NEK6 can serve as a new therapeutic candidate for OC and that NEK6 inhibition may be an effective strategy for OC treatment.

摘要

卵巢癌(OC)是女性生殖器官常见的恶性肿瘤。新型丝氨酸/苏氨酸激酶NEK6在多种癌症中高表达,并影响患者的预后。然而,NEK6在OC中的作用仍不清楚。在本研究中,我们调查了NEK6在OC中的表达谱及其在OC发生发展中的作用。通过生物信息学分析探索了NEK6在各种癌症和OC中的表达谱,并通过免疫组织化学(IHC)染色检测其在OC患者中的表达。还分析了其表达与临床病理因素之间的相关性。此外,通过RT-qPCR和蛋白质免疫印迹法检测OC患者肿瘤组织中的NEK6水平。分别使用MTT、Transwell和流式细胞术分析细胞生长、迁移、侵袭和凋亡等生物学功能。生物信息学分析显示,NEK6在包括OC在内的大多数人类癌症中高表达。IHC显示肿瘤组织中67.27%为中度或强NEK6染色,32.73%(36/110)为弱染色,正常卵巢组织中为阴性或弱NEK6染色,其高表达与组织学分级(=0.008)和转移(=0.006)等临床病理因素相关。Kaplan-Meier生存曲线显示,NEK6高表达的OC患者总生存率较差(=0.025)。NEK6在OC组织以及SK-OV-3和A2780细胞中过表达,当用小干扰RNA敲低NEK6时,细胞生长、迁移和侵袭受到抑制,而细胞凋亡显著促进。NEK6在OC中高表达;其过表达提示预后不良;敲低NEK6导致生长、迁移和侵袭受到抑制,同时促进OC细胞凋亡。这些发现表明,NEK6是OC中的潜在癌基因和不良预后因素,提示NEK6可作为OC的新治疗靶点,抑制NEK6可能是OC治疗的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67de/11786049/df94fd6f42c8/jcav16p1335g001.jpg

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