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miR-107 通过靶向 NSG1 调控 ERK 通路抑制下咽鳞癌细胞的进展。

miR-107 Targets NSG1 to Regulate Hypopharyngeal Squamous Cell Carcinoma Progression through ERK Pathway.

机构信息

Department of Otolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

Sleep Medicine Centre, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

出版信息

Int J Mol Sci. 2024 May 29;25(11):5961. doi: 10.3390/ijms25115961.

Abstract

Hypopharyngeal squamous cell carcinoma (HSCC) is a kind of malignant tumor with a poor prognosis and low quality of life in the otolaryngology department. It has been found that microRNA (miRNA) plays an important role in the occurrence and development of various tumors. This study found that the expression level of miRNA-107 (miR-107) in HSCC was significantly reduced. Subsequently, we screened out the downstream direct target gene Neuronal Vesicle Trafficking Associated 1 (NSG1) related to miR-107 through bioinformatics analysis and found that the expression of NSG1 was increased in HSCC tissues. Following the overexpression of miR-107 in HSCC cells, it was observed that miR-107 directly suppressed NSG1 expression, leading to increased apoptosis, decreased proliferation, and reduced invasion capabilities of HSCC cells. Subsequent experiments involving the overexpression and knockdown of NSG1 in HSCC cells demonstrated that elevated NSG1 levels enhanced cell proliferation, migration, and invasion, while the opposite effect was observed upon NSG1 knockdown. Further investigations revealed that changes in NSG1 levels in the HSCC cells were accompanied by alterations in ERK signaling pathway proteins, suggesting a potential regulatory role of NSG1 in HSCC cell proliferation, migration, and invasion through the ERK pathway. These findings highlight the significance of miR-107 and NSG1 in hypopharyngeal cancer metastasis, offering promising targets for therapeutic interventions and prognostic evaluations for HSCC.

摘要

下咽鳞状细胞癌(HSCC)是耳鼻喉科中一种预后差、生活质量低的恶性肿瘤。已经发现微小 RNA(miRNA)在各种肿瘤的发生和发展中起着重要作用。本研究发现 miRNA-107(miR-107)在下咽鳞状细胞癌中的表达水平显著降低。随后,我们通过生物信息学分析筛选出与 miR-107 相关的下游直接靶基因神经元囊泡转运相关蛋白 1(NSG1),并发现 NSG1 在 HSCC 组织中的表达增加。在 HSCC 细胞中过表达 miR-107 后,观察到 miR-107 直接抑制 NSG1 的表达,导致 HSCC 细胞凋亡增加、增殖减少和侵袭能力降低。随后在 HSCC 细胞中进行的 NSG1 过表达和敲低实验表明,NSG1 水平的升高增强了细胞的增殖、迁移和侵袭能力,而 NSG1 敲低则观察到相反的效果。进一步的研究表明,HSCC 细胞中 NSG1 水平的变化伴随着 ERK 信号通路蛋白的改变,表明 NSG1 通过 ERK 通路在下咽鳞状细胞癌细胞增殖、迁移和侵袭中可能具有调节作用。这些发现强调了 miR-107 和 NSG1 在下咽癌转移中的重要性,为 HSCC 的治疗干预和预后评估提供了有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7af3/11172869/8db8ebe6932b/ijms-25-05961-g001.jpg

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