N4BP3通过与XPO1相互作用激活Wnt/β-catenin信号通路,促进卵巢癌进展和紫杉醇耐药。

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Mingliang Fan , Ke Liu , Yonggang Shi , Jie Hao , Haifeng Qiu , Yan Liang
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引用次数: 0

摘要

卵巢癌是世界范围内一种高致死率的妇科恶性肿瘤,主要原因是晚期诊断和化疗耐药。nedd4结合蛋白3 (N4BP3)已被确定在几种癌症的发展中起作用。然而,它在卵巢癌中的作用尚不清楚。通过生物信息学分析分析N4BP3在卵巢癌中的表达谱及其与患者预后的关系。N4BP3的表达在卵巢癌细胞系中得到证实。随后,通过调控N4BP3的表达来研究其对卵巢癌细胞恶性表型的影响。此外,建立紫杉醇(PTX)耐药细胞系,检测N4BP3对PTX耐药的影响。在体内进一步分析N4BP3对肿瘤生长和PTX耐药的影响。采用生物信息学分析、免疫共沉淀和Western blot方法探讨N4BP3的潜在作用机制。我们发现N4BP3在卵巢癌组织中高表达,N4BP3高表达的患者总生存期和无进展生存期较短。N4BP3在卵巢癌细胞系中表达较高,在ptx耐药细胞中表达更高。上调N4BP3可显著促进卵巢癌细胞的增殖和侵袭,提高PTX耐药性,下调N4BP3则相反。在异种移植小鼠模型中,沉默N4BP3抑制肿瘤生长并降低PTX耐药性。机制上,N4BP3通过与XPO1结合激活Wnt/β-catenin信号传导。综上所述,N4BP3通过与XPO1相互作用激活Wnt/β-catenin信号通路,促进卵巢癌进展和PTX耐药。N4BP3可能作为卵巢癌治疗的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
N4BP3 promotes ovarian cancer progression and paclitaxel resistance by activating the Wnt/β-catenin signaling through interaction with XPO1
Ovarian cancer is a highly lethal gynecological malignancy worldwide, primarily attributed to late diagnosis and chemoresistance. The Nedd4-binding protein 3 (N4BP3) has been identified to function in the development of several cancers. However, its role in ovarian cancer remains unclear. The expression profile of N4BP3 and its association with patients' prognosis in ovarian cancer was analyzed through bioinformatic analysis. N4BP3 expression was confirmed in ovarian cancer cell lines. Subsequently, N4BP3 expression was manipulated to investigate its effects on the malignant phenotypes of ovarian cancer cells. Furthermore, paclitaxel (PTX)-resistant cell lines were established to examine N4BP3's influence on PTX resistance. The effects of N4BP3 on tumor growth and PTX resistance were further analyzed in vivo. The potential mechanisms of N4BP3 were explored using bioinformatic analysis, co-immunoprecipitation, and Western blot. We found that N4BP3 was highly expressed in ovarian cancer tissues, and patients with higher N4BP3 expression exhibited shorter overall survival and progression-free survival. N4BP3 expression was higher in ovarian cancer cell lines, with even higher levels in PTX-resistant cells. Upregulation of N4BP3 significantly promoted the proliferation and invasion, and elevated PTX resistance in ovarian cancer cells, while its downregulation had the opposite effects. Silencing of N4BP3 inhibited tumor growth and decreased PTX resistance in a xenograft mouse model. Mechanistically, N4BP3 activated the Wnt/β-catenin signaling through binding to XPO1. Taken together, N4BP3 promotes ovarian cancer progression and PTX resistance by activating the Wnt/β-catenin signaling through interaction with XPO1. N4BP3 may serve as a potential therapeutic target for the treatment of ovarian cancer.
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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