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文章:

SOX2-OT与ILF3结合通过调控STAT3与TGF-β信号通路间的交互作用促进头颈癌进展

SOX2-OT Binds with ILF3 to Promote Head and Neck Cancer Progression by Modulating Crosstalk between STAT3 and TGF-β Signaling

原文发布日期:8 December 2023

DOI: 10.3390/cancers15245766

类型: Article

开放获取: 是

 

英文摘要:

Long non-coding RNA (lncRNA) is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The molecular mechanism of lncRNA SOX2-OT in HNSCC remains unclear. Therefore, we aimed to elucidate the oncogenic role of SOX2-OT in HNSCC. QRT-PCR analysis was performed in 61 pairs of HNSCC cancer tissues, adjacent normal tissues, and 68 plasma samples confirmed that lncRNA SOX2-OT was overexpressed in cancer tissues and plasma samples, which served as a poor prognostic factor for HNSCC. The FISH assay demonstrated that SOX2-OT was localized in the nucleus and cytoplasm of HNSCC cell lines. Further, the cell function assay confirmed that SOX2-OT promoted cell proliferation and metastasis in vitro and in vivo. RNA pulldown and RIP assay results revealed that SOX2-OT bonds with ILF3 in HNSCC, and the rescue assay confirmed that SOX2-OT played an oncogenic role depending on ILF3 protein expression. Ingenuity pathway analysis and Western blotting indicated that SOX2-OT regulated HNSCC progression by promoting STAT3 phosphorylation and modulating the crosstalk between STAT3 and TGF-β signaling. These results reveal evidence for the role of SOX2-OT in HNSCC progression and metastasis by binding to ILF3, which may serve as a therapeutic target and prognostic biomarker in HNSCC.

 

摘要翻译: 

长链非编码RNA(lncRNA)参与头颈部鳞状细胞癌(HNSCC)的进展过程。目前,lncRNA SOX2-OT在HNSCC中的分子机制尚不明确。因此,本研究旨在阐明SOX2-OT在HNSCC中的致癌作用。通过对61对HNSCC癌组织与癌旁正常组织以及68例血浆样本进行实时定量PCR分析,证实SOX2-OT在癌组织和血浆样本中均呈现过表达,且其高表达与HNSCC不良预后相关。荧光原位杂交实验显示,SOX2-OT定位于HNSCC细胞系的细胞核与细胞质中。进一步的细胞功能实验证实,SOX2-OT在体内外均能促进细胞增殖与转移。RNA pull-down与RNA免疫沉淀实验结果表明,SOX2-OT在HNSCC中与ILF3蛋白结合,而挽救实验证实SOX2-OT的致癌作用依赖于ILF3蛋白的表达。通路分析与蛋白质印迹实验表明,SOX2-OT通过促进STAT3磷酸化并调控STAT3与TGF-β信号通路间的交互作用,从而调控HNSCC的进展。这些结果揭示了SOX2-OT通过与ILF3结合在HNSCC进展和转移中的作用机制,提示其可能成为HNSCC的治疗靶点与预后生物标志物。

 

原文链接:

SOX2-OT Binds with ILF3 to Promote Head and Neck Cancer Progression by Modulating Crosstalk between STAT3 and TGF-β Signaling

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