The American Journal of Pathology ( IF 4.7 ) Pub Date : 2023-01-23 , DOI: 10.1016/j.ajpath.2022.10.010
Zushi Geng 1 , Yinzhen Huang 2 , Shuang Wu 2 , Dandan Zhu 2 , Wenlu Li 2
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As a common type of head and neck squamous cell carcinoma, oral squamous cell carcinoma (OSCC) is a lethal and deforming disease. Long noncoding RNAs have emerged as critical modulators in different malignancies. However, the role of fucosyltransferase 8 antisense RNA 1 (FUT8-AS1) in OSCC still remains elusive. In this study, quantitative RT-PCR and Western blot were used for the measurement of RNAs and proteins. Mechanism assays explored the putative correlation among genes. In vitro assays evaluated the changes in OSCC cell malignant phenotype, whereas in vivo assays highlighted the influence of FUT8-AS1 on tumor growth. FUT8-AS1, aberrantly up-regulated in OSCC tissues and cells, could exacerbate OSCC cell malignant behaviors. The cancerogenic property of FUT8-AS1 in OSCC was further confirmed via animal experiments. Furthermore, FUT8-AS1 enhanced the expression of transcription factor 4 (TCF4) via sponging miR-944 and recruiting fused in sarcoma (FUS), thus affecting OSCC cell biological behaviors via modulation on Wnt/β-catenin signaling activity. In addition, TCF4 was validated as the transcriptional activator of FUT8-AS1. To conclude, TCF4-mediated FUT8-AS1 could exacerbate OSCC cell malignant behaviors and facilitate tumor growth via modulation on miR-944/FUS/TCF4.
中文翻译:

FUT8-AS1/miR-944/Fused in Sarcoma/Transcription Factor 4 Feedback Loop 通过激活 Wnt/β-Catenin 信号通路参与口腔鳞状细胞癌的发展
作为头颈部鳞状细胞癌的常见类型,口腔鳞状细胞癌 (OSCC) 是一种致死性和畸形性疾病。长链非编码 RNA 已成为不同恶性肿瘤的关键调节剂。然而,岩藻糖基转移酶 8 反义 RNA 1 ( FUT8-AS1 ) 在 OSCC 中的作用仍不清楚。在这项研究中,定量 RT-PCR 和蛋白质印迹被用于 RNA 和蛋白质的测量。机制分析探索了基因之间的假定相关性。体外测定评估了 OSCC 细胞恶性表型的变化,而体内测定突出了FUT8-AS1对肿瘤生长的影响。FUT8-AS1, 在 OSCC 组织和细胞中异常上调,可加剧 OSCC 细胞的恶性行为。通过动物实验进一步证实了FUT8-AS1在 OSCC 中的致癌特性。此外,FUT8-AS1通过海绵化 miR-944 和募集融合肉瘤 (FUS) 增强转录因子 4 (TCF4) 的表达,从而通过调节 Wnt/β-catenin 信号活性影响 OSCC 细胞生物学行为。此外,TCF4 被验证为FUT8-AS1的转录激活因子。总之,TCF4 介导的FUT8-AS1可加剧 OSCC 细胞的恶性行为,并通过调节 miR-944/FUS/TCF4 促进肿瘤生长。