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环状RNA circSLC7A11通过从LASP1中吸附miR-877-5p促进喉鳞状细胞癌的进展和干性。

Circular RNA circSLC7A11 contributes to progression and stemness of laryngeal squamous cell carcinoma via sponging miR-877-5p from LASP1.

作者信息

Yu Wenjie, He Xiaoling, Zhang Chunming, Huang Fuhui

机构信息

Department of Otolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University, China.

出版信息

Heliyon. 2023 Jul 14;9(7):e18290. doi: 10.1016/j.heliyon.2023.e18290. eCollection 2023 Jul.

Abstract

BACKGROUND

Laryngeal squamous cell carcinoma (LSCC) belongs to tumors of head and neck. Circular RNA circSLC7A11 functions as oncogenes in various tumors. However, the role of circSLC7A11 in LSCC remains largely unknown. Here, we aimed to clarify the circSLC7A11 function in LSCC.

METHODS

Relevance between circSLC7A11 expressions and LSCC clinicopathological was checked using chi-square. Relevance between circSLC7A11 expressions and LSCC patients' survival time was validated using Kaplan-Meier analysis. CircSLC7A11 expressions in LSCC tissues and cells were determined using quantitative real-time PCR. CircSLC7A11 functions in LSCC were examined by Cell Counting Kit-8, EdU analysis, Western blot, flow cytometry, sphere formation assay, and Transwell analysis. Meanwhile, circSLC7A11 mechanism in LSCC was determined using dual-luciferase reporter analysis, RNA pull-down, RNA Immunoprecipitation.

RESULTS

CircSLC7A11 was highly expressed in LSCC, and high circSLC7A11 expressions were interrelated to the TNM stage. Also, LSCC patients with high circSLC7A11 owned shorter overall survival. Functional studies revealed that circSLC7A11 knockdown reduced LSCC cell proliferation, migration, invasion, stemness characteristics, and enhanced cell apoptosis. Mechanistic study data corroborated that circSLC7A11 targeted miR-877-5p, miR-877-5p targeted LASP1. LASP1 was negatively interrelated to miR-877-5p and was positively interrelated to circSLC7A11 in LSCC tissues. Also, circSLC7A11 knockdown reduced the LASP1 levels, and miR-877-5p inhibitor co-transfection reversed this reduction. Rescue assays further demonstrated that circSLC7A11 accelerated LSCC through miR-877-5p/LASP1.

CONCLUSION

CircSLC7A11 exerted oncogenic functions in LSCC by miR-877-5p/LASP1, hinting that circSLC7A11 was a novel biomarker for LSCC.

摘要

背景

喉鳞状细胞癌(LSCC)属于头颈部肿瘤。环状RNA circSLC7A11在多种肿瘤中发挥癌基因作用。然而,circSLC7A11在LSCC中的作用在很大程度上仍不清楚。在此,我们旨在阐明circSLC7A11在LSCC中的功能。

方法

使用卡方检验检查circSLC7A11表达与LSCC临床病理之间的相关性。使用Kaplan-Meier分析验证circSLC7A11表达与LSCC患者生存时间之间的相关性。使用定量实时PCR测定LSCC组织和细胞中circSLC7A11的表达。通过细胞计数试剂盒-8、EdU分析、蛋白质免疫印迹法、流式细胞术、成球实验和Transwell分析检测circSLC7A11在LSCC中的功能。同时,使用双荧光素酶报告基因分析、RNA下拉实验、RNA免疫沉淀法确定circSLC7A11在LSCC中的作用机制。

结果

circSLC7A11在LSCC中高表达,且circSLC7A11高表达与TNM分期相关。此外,circSLC7A11高表达的LSCC患者总生存期较短。功能研究表明,circSLC7A11敲低可降低LSCC细胞增殖、迁移、侵袭、干性特征,并增强细胞凋亡。机制研究数据证实,circSLC7A11靶向miR-877-5p,miR-877-5p靶向LASP1。在LSCC组织中,LASP1与miR-877-5p呈负相关,与circSLC7A11呈正相关。此外,circSLC7A11敲低降低了LASP1水平,而共转染miR-877-5p抑制剂可逆转这种降低。挽救实验进一步证明,circSLC7A11通过miR-877-5p/LASP1促进LSCC进展。

结论

circSLC7A11通过miR-877-5p/LASP1在LSCC中发挥致癌作用,提示circSLC7A11是LSCC的一种新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e0/10393633/882435ff76ca/gr1.jpg

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