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circIGHG 通过 miR-142-5p/IGF2BP3 信号通路诱导上皮间质转化促进口腔鳞状细胞癌进展。

circIGHG-Induced Epithelial-to-Mesenchymal Transition Promotes Oral Squamous Cell Carcinoma Progression via miR-142-5p/IGF2BP3 Signaling.

机构信息

Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong, China.

出版信息

Cancer Res. 2021 Jan 15;81(2):344-355. doi: 10.1158/0008-5472.CAN-20-0554. Epub 2020 Nov 17.

Abstract

Circular RNAs (circRNA) are a new member of endogenously produced noncoding RNAs that have been characterized as key regulators of gene expression in a variety of malignances. However, the role of circRNA in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we identified unique circRNA that regulate OSCC progression and metastasis and pave roads for future research in early diagnosis, prevention, and treatment of OSCC. Transcriptomic analyses identified a circRNA derived from locus () as significantly upregulated in OSCC and positively associated with poor prognosis of OSCC. directly bound and consequently elevated IGF2BP3 activity. Knockdown of led to impaired expression of IGF2BP3 and attenuated aggressiveness of OSCC cells. Epithelial-mesenchymal transition was the main mechanism through which /IGF2BP3 promotes metastasis of OSCC. Overall, these results demonstrate that circIGHG plays a pivotal role in OSCC development and metastasis and has potential to serve as a biomarker and therapeutic target for early-stage diagnosis and treatment of OSCC. SIGNIFICANCE: These findings broaden our insights regarding regulation of OSCC progression by circular RNA and serve as a reference for future clinical research in OSCC diagnosis and treatment.

摘要

环状 RNA(circRNA)是内源性产生的非编码 RNA 的新成员,已被证明是多种恶性肿瘤中基因表达的关键调控因子。然而,circRNA 在口腔鳞状细胞癌(OSCC)中的作用在很大程度上仍不清楚。在本研究中,我们鉴定了具有独特功能的 circRNA,它们调节 OSCC 的进展和转移,为 OSCC 的早期诊断、预防和治疗的未来研究铺平了道路。转录组分析鉴定出一个来自 ()基因的 circRNA 在 OSCC 中显著上调,并与 OSCC 的不良预后呈正相关。 直接结合 ,从而提高 IGF2BP3 的活性。 的敲低导致 IGF2BP3 的表达受损,并减弱了 OSCC 细胞的侵袭能力。上皮-间充质转化是 /IGF2BP3 促进 OSCC 转移的主要机制。总之,这些结果表明 circIGHG 在 OSCC 的发展和转移中起着关键作用,并有可能作为 OSCC 早期诊断和治疗的生物标志物和治疗靶点。意义:这些发现拓宽了我们对环状 RNA 调控 OSCC 进展的认识,为 OSCC 的临床诊断和治疗研究提供了参考。

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