Exosomes carrying lncRNA FLG-AS1 overexpression vectors inhibit the tumorigenesis of oral squamous cell carcinoma via fat mass and obesity-associated protein-mediated m6A modification.

IF 2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Cytotechnology Pub Date : 2025-08-01 Epub Date: 2025-07-01 DOI:10.1007/s10616-025-00801-y
Xiaoyang Xia, Yan Liu
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引用次数: 0

Abstract

Long noncoding RNAs (lncRNAs) selectively incorporated into exosomes contribute to the tumorigenesis of various cancers. However, the role of the lncRNA FLG-AS1 in oral squamous cell carcinoma (OSCC) has yet to be investigated. Hence, the current study aimed to evaluate the potential role of exosome-derived FLG-AS1 in OSCC. The expression of FLG-AS1 and fat mass and obesity-associated protein (FTO) in OSCC samples were determined via real-time quantitative polymerase chain reaction (RT-qPCR). The role of FLG-AS1 in OSCC was investigated by performing CCK8, flow cytometry, and transwell assays. Additionally, bioinformatics, methylated (m6A) RNA immunoprecipitation, and RT-qPCR were performed to evaluate the n6-methyladenosine (m6A) modification of FLG-AS1 and its underlying mechanism. Characterization of exosomal FLG-AS1 in OSCC cells was achieved through transmission electron microscopy, nanoparticle tracking analysis, Western blot analysis of CD63 and CD9, and RT-qPCR. Finally, the effects of exosomal FLG-AS1 on OSCC cell malignancy was analyzed using the aforementioned cell-based assays. Overall, our findings showed that low FLG-AS1 expression in OSCC restricted the malignant properties of OSCC cells. Furthermore, FTO reduced FLG-AS1 expression by mediating its m6A demethylation in OSCC cells. Exosomal FLG-AS1 expression was upregulated in OSCC cells, suggesting that it was packaged in the OSCC cell-derived exosomes, whereas exosome-derived FLG-AS1 overexpression vector reduced the malignant potential of the target OSCC cells. In conclusion, exosomal FLG-AS1 functions as a tumor suppressor in OSCC, while FTO can impair FLG-AS1 expression through m6A demethylation.

携带lncRNA FLG-AS1过表达载体的外泌体通过脂肪团和肥胖相关蛋白介导的m6A修饰抑制口腔鳞状细胞癌的肿瘤发生。
长链非编码rna (lncRNAs)选择性地整合到外泌体中,有助于各种癌症的肿瘤发生。然而,lncRNA FLG-AS1在口腔鳞状细胞癌(OSCC)中的作用尚未被研究。因此,本研究旨在评估外泌体衍生的FLG-AS1在OSCC中的潜在作用。采用实时定量聚合酶链式反应(RT-qPCR)检测OSCC样品中FLG-AS1和脂肪质量及肥胖相关蛋白(FTO)的表达。通过CCK8、流式细胞术和transwell实验研究FLG-AS1在OSCC中的作用。此外,我们还利用生物信息学、甲基化(m6A) RNA免疫沉淀和RT-qPCR来评估FLG-AS1的n6-甲基腺苷(m6A)修饰及其潜在机制。通过透射电镜、纳米颗粒跟踪分析、CD63和CD9的Western blot分析和RT-qPCR对OSCC细胞外泌体FLG-AS1进行表征。最后,使用上述基于细胞的检测分析外泌体FLG-AS1对OSCC细胞恶性肿瘤的影响。总之,我们的研究结果表明,在OSCC中,FLG-AS1的低表达限制了OSCC细胞的恶性特性。此外,FTO通过介导OSCC细胞中的m6A去甲基化来降低FLG-AS1的表达。外泌体FLG-AS1在OSCC细胞中的表达上调,提示其被包装在OSCC细胞衍生的外泌体中,而外泌体衍生的FLG-AS1过表达载体降低了靶OSCC细胞的恶性潜能。综上所述,外泌体FLG-AS1在OSCC中发挥抑癌作用,而FTO可通过m6A去甲基化损害FLG-AS1的表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cytotechnology
Cytotechnology 生物-生物工程与应用微生物
CiteScore
4.10
自引率
0.00%
发文量
49
审稿时长
6-12 weeks
期刊介绍: The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.
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