Microrna-382-5p靶向YBX1通过调节RAS/MAPK信号传导促进喉鳞状细胞癌的进展

IF 2.5 4区 医学 Q3 ONCOLOGY
Wen Zeng, Yiyun Pan, Hailong Chen, Xianhua Lei, Xiangmin Zhang
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引用次数: 0

摘要

喉部鳞状细胞癌是头颈部最常见的癌症。Y-box结合蛋白-1 (YBX1)在某些类型的癌症中具有促肿瘤作用。然而,它在LSCC中的作用仍然未知。本研究旨在确定YBX1在LSCC中的作用,通过基因表达综合数据库(GEO)的生物信息学分析和我们的队列数据来探索YBX1表达与LSCC临床病理因素的关系。然后,构建稳定或瞬时转染质粒或siRNA的细胞,评估YBX1的缺失和获得对体外LSCC细胞生物学表型的影响。此外,还建立了皮下异种移植和原位肝肿瘤小鼠模型进行验证。使用查询的miRNA数据库和随后的荧光素酶报告基因检测来确认YBX1的miR-382-5p靶点。最后,利用TGCA数据中的KEGG富集注释对miR-382-5p/YBX1进行下游分析,并通过pcr和Western免疫印迹验证。结果表明,YBX1在LSCC肿瘤中显著上调与TNM分期晚期和预后不良相关。YBX1基因的敲低明显损害了Tu212细胞的增殖、侵袭和迁移活性。我们证实了miR-382-5p在体外和体内靶向YBX1介导LSCC的进展。我们进一步证实mir -382-5p/YBX1通过调节Ras/MAPK信号轴调控LSCC的进展。综上所述,我们的研究结果表明YBX1是LSCC进展的重要促进因子。miR-382-5p/YBX1/RAS/MAPK信号通路可以被认为是治疗LSCC的有希望的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
YBX1, Targeted By Microrna-382-5p, Promotes Laryngeal Squamous Cell Carcinoma Progression via Modulating RAS/MAPK Signaling.

Background: Laryngeal squamous cell carcinoma (LSCC) is the most common cancer of head and neck cancer. Y-box binding protein-1 (YBX1) has tumor-promoting effects in some types of cancers. However, its role in LSCC remains unknown. This study set out to identify the role of YBX1 in LSCC.

Methods: Bioinformatics analysis of the Gene Expression Omnibus (GEO) database and our cohort data were used to explore the association of YBX1 expression with clinicopathological factors in LSCC. Then, cells with stably or transiently transfected with plasmid or siRNA were constructed to assess the effect of loss and gain of YBX1 on the biological phenotypes of LSCC cells in vitro. In addition, subcutaneous xenograft and orthotopic liver tumor mouse models were constructed for validation. The interrogated miRNA databases and subsequent luciferase reporter assays were used to confirm the miR-382-5p target of YBX1. At last, KEGG enrichment annotation from TGCA data was used for downstream analyses of miR-382-5p/YBX1 and verified by PCR and Western immunoblotting.

Results: The results showed that significant upregulation of YBX1 in LSCC tumors was correlated with advanced TNM stage and poor prognosis. Knockdown of YBX1 markedly impaired the proliferative, invasive, and migratory activity of Tu212 cells. We confirmed that miR-382-5p targets YBX1 to mediate LSCC progression both in vitro and in vivo. We further confirmed that miR-382-5p/YBX1 modulated the Ras/MAPK signaling axis to regulate the progression of LSCC.

Conclusion: Together, our results indicated that YBX1 is an important promoter of LSCC progression. And miR-382-5p/YBX1/RAS/MAPK signaling pathway can be perceived as a promising target in the treatment of LSCC.

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来源期刊
CiteScore
4.50
自引率
7.10%
发文量
55
审稿时长
3 months
期刊介绍: Aims & Scope Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.
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