Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis

Author:

Wu Yongyan,Zhang Yuliang,Zheng Xiwang,Dai Fengsheng,Lu Yan,Dai Li,Niu Min,Guo Huina,Li Wenqi,Xue Xuting,Bo Yunfeng,Guo Yujia,Qin Jiangbo,Qin Yixiao,Liu Hongliang,Zhang Yu,Yang Tao,Li Li,Zhang Linshi,Hou Rui,Wen Shuxin,An Changming,Li Huizheng,Xu Wei,Gao WeiORCID

Abstract

Abstract Background Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck. LSCC patients have seriously impaired vocal, respiratory, and swallowing functions with poor prognosis. Circular RNA (circRNA) has attracted great attention in cancer research. However, the expression patterns and roles of circRNAs in LSCC remain largely unknown. Methods RNA sequencing was performed on 57 pairs of LSCC and matched adjacent normal mucosa tissues to construct circRNA, miRNA, and mRNA expression profiles. RT-PCR, qPCR, Sanger sequencing, and FISH were undertaken to study the expression, localization, and clinical significance of circCORO1C in LSCC tissues and cells. The functions of circCORO1C in LSCC were investigated by RNAi-mediated knockdown, proliferation analysis, EdU staining, colony formation assay, Transwell assay, and apoptosis analysis. The regulatory mechanisms among circCORO1C, let-7c-5p, and PBX3 were investigated by luciferase assay, RNA immunoprecipitation, western blotting, and immunohistochemistry. Results circCORO1C was highly expressed in LSCC tissues and cells, and this high expression was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circCORO1C inhibited the proliferation, migration, invasion, and in vivo tumorigenesis of LSCC cells. Mechanistic studies revealed that circCORO1C competitively bound to let-7c-5p and prevented it from decreasing the level of PBX3, which promoted the epithelial–mesenchymal transition and finally facilitated the malignant progression of LSCC. Conclusions circCORO1C has an oncogenic role in LSCC progression and may serve as a novel target for LSCC therapy. circCORO1C expression has the potential to serve as a novel diagnostic and prognostic biomarker for LSCC detection.

Funder

National Natural Science Foundation of China

Postdoctoral Research Foundation of China

The Excellent talent science and technology innovation project of Shanxi Province

Youth Science and Technology Research Fund of Shanxi Province

Shanxi Province Scientific and Technological Achievements Transformation Guidance Foundation

Youth Foundation of The First Hospital Affiliated with Shanxi Medical University

Youth Top Talent Program Fund of Shanxi Province

Fund of Shanxi “1331” Project

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Oncology,Molecular Medicine

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