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环状RNA_ACAP2通过靶向miR-21-5p/STAT3信号轴抑制头颈部鳞状细胞癌中的上皮-间质转化

CircRNA_ACAP2 Suppresses EMT in Head and Neck Squamous Cell Carcinoma by Targeting the miR-21-5p/STAT3 Signaling Axis.

作者信息

Ma Chuan, Shi Tingting, Qu Zhuli, Zhang Aobo, Wu Zuping, Zhao Huaqiang, Zhao Haoming, Chen Hongyu

机构信息

Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China.

Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

出版信息

Front Oncol. 2020 Dec 11;10:583682. doi: 10.3389/fonc.2020.583682. eCollection 2020.

Abstract

Circular RNAs (circRNAs) contain microRNA (miRNA)-specific binding sites and can function as miRNA sponges to regulate gene expression by suppressing the inhibitory effect of miRNAs on their target genes. MiR-21-5p has been reported to be involved in the development of head and neck squamous cell carcinoma (HNSCC) and plays an important role in the activation of epithelial-mesenchymal transition (EMT). However, the upstream regulatory mechanism and downstream targets of miR-21-5p in tumor cells remain unknown. CircRNA_ACAP2 inhibits the function of miR-21-5p by binding to its specific binding sites in HNSCC cells. Overexpression of CircRNA_ACAP2 inhibits the proliferation and migration of HNSCC cells, while downregulation of CircRNA_ACAP2 has the opposite effect. STAT3 is a direct target gene of miR-21-5p and a transcription factor of ZEB1. We demonstrate that CircRNA_ACAP2 functions as a tumor suppressor gene in HNSCC and that its function is regulated the miR-21-5p/STAT3 signaling axis.

摘要

环状RNA(circRNAs)含有微小RNA(miRNA)特异性结合位点,可作为miRNA海绵,通过抑制miRNA对其靶基因的抑制作用来调节基因表达。据报道,miR-21-5p参与头颈部鳞状细胞癌(HNSCC)的发生发展,并在上皮-间质转化(EMT)激活中起重要作用。然而,miR-21-5p在肿瘤细胞中的上游调控机制和下游靶点仍不清楚。CircRNA_ACAP2通过与HNSCC细胞中的特定结合位点结合来抑制miR-21-5p的功能。CircRNA_ACAP2的过表达抑制HNSCC细胞的增殖和迁移,而CircRNA_ACAP2的下调则产生相反的效果。STAT3是miR-21-5p的直接靶基因和ZEB1的转录因子。我们证明CircRNA_ACAP2在HNSCC中作为肿瘤抑制基因发挥作用,其功能受miR-21-5p/STAT3信号轴调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b5/7759648/8e0b68f60d7c/fonc-10-583682-g001.jpg

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