Overexpressed NEK2 contributes to progression and cisplatin resistance through activating the Wnt/β-catenin signaling pathway in cervical cancer.

IF 5.3 2区 医学 Q1 ONCOLOGY
Jiang Haiye, Wang Xiangzhu, Zhang Yunfei, Gui Shumin, Ni Chang, Jiang Yaohui, Yin Heng, Nie Xinmin
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Abstract

Background: Cervical cancer ranks as the fourth most common cancer among women, with cisplatin resistance posing a significant challenge to the long-term survival of patients.

Methods: The roles of NEK2 in cervical cancer were examined through bioinformatics analysis. Transfection efficiency and molecular mechanisms were assessed using real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting (WB). To evaluate cell functions, a series of assays, including cell counting kit-8 (CCK-8), wound healing, transwell, colony formation, and flow cytometry (FCM), were performed on HeLa, SiHa, and HeLa/DDP (cisplatin-resistant) cell lines.

Results: We found that NEK2 is upregulated in cervical cancer tissues compared to normal tissues and is further elevated in cisplatin-resistant cervical cancer compared to cisplatin-sensitive cases. The overexpression of NEK2 is associated with enhanced cancer progression, poorer prognosis, and increased cisplatin resistance in cervical cancer patients. Notably, in the presence of cisplatin, the knockdown of NEK2 inhibited cell viability, proliferation, migration, invasion, and G2/M phase arrest in cervical cancer cells, while also enhancing the sensitivity of cisplatin-resistant cervical cancer cells through the inactivation of the Wnt/β-catenin signaling pathway.

Conclusions: NEK2 is upregulated in cervical squamous cell carcinoma (CESC) compared to normal tissues and exhibits higher levels in cisplatin-resistant CESC than in sensitive counterparts, correlating with disease progression and poor prognosis. Thus, NEK2 is implicated in the cisplatin resistance of CESC via the activation of the Wnt/β-catenin signaling pathway, suggesting its potential as a prognostic marker and a novel target for the diagnosis and treatment of cisplatin-resistant CESC.

过表达的NEK2通过激活Wnt/β-catenin信号通路参与宫颈癌的进展和顺铂耐药。
背景:宫颈癌是女性最常见的第四大癌症,顺铂耐药对患者的长期生存构成了重大挑战。方法:通过生物信息学分析探讨NEK2在宫颈癌中的作用。采用实时定量聚合酶链反应(qRT-PCR)和western blotting (WB)技术评估转染效率和分子机制。为了评估细胞功能,对HeLa、SiHa和HeLa/DDP(顺铂耐药)细胞系进行了一系列检测,包括细胞计数试剂盒-8 (CCK-8)、伤口愈合、transwell、菌落形成和流式细胞术(FCM)。结果:我们发现,与正常组织相比,NEK2在宫颈癌组织中上调,在顺铂耐药的宫颈癌中,与顺铂敏感的病例相比,NEK2进一步升高。在宫颈癌患者中,NEK2的过表达与癌症进展加快、预后较差以及顺铂耐药性增加有关。值得注意的是,在顺铂存在的情况下,NEK2的敲低抑制了宫颈癌细胞的活力、增殖、迁移、侵袭和G2/M期阻滞,同时也通过Wnt/β-catenin信号通路的失活增强了顺铂耐药宫颈癌细胞的敏感性。结论:与正常组织相比,宫颈鳞状细胞癌(CESC)中NEK2表达上调,顺铂耐药CESC中NEK2表达水平高于敏感组织,与疾病进展和不良预后相关。因此,NEK2通过激活Wnt/β-catenin信号通路与CESC的顺铂耐药有关,这表明它有可能作为一种预后标志物和诊断和治疗顺铂耐药CESC的新靶点。
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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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