Int J Biol Sci 2022; 18(5):2116-2131. doi:10.7150/ijbs.66770 This issue

Research Paper

CircRAPGEF5 Promotes the Proliferation and Metastasis of Lung Adenocarcinoma through the miR-1236-3p/ZEB1 Axis and Serves as a Potential Biomarker

Huixin Zhou1, Xiaolu Huang1, Xiang Yang1, Feng Jiang1, Fanggui Shao1, Wenjing Shi1, Kate Huang2, Jingjing Pan1, Yan Zhang1, Jie Chen3✉, Yumin Wang1✉

1. Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325000, China
2. Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
3. Department of Intensive Care Unit, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China

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Citation:
Zhou H, Huang X, Yang X, Jiang F, Shao F, Shi W, Huang K, Pan J, Zhang Y, Chen J, Wang Y. CircRAPGEF5 Promotes the Proliferation and Metastasis of Lung Adenocarcinoma through the miR-1236-3p/ZEB1 Axis and Serves as a Potential Biomarker. Int J Biol Sci 2022; 18(5):2116-2131. doi:10.7150/ijbs.66770. Available from https://www.ijbs.com/v18p2116.htm

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Abstract

Graphic abstract

Lung adenocarcinoma (LAD) is a common malignancy; however, its underlying molecular mechanism is unclear. Circular RNAs (circRNAs) serve as significant cancer regulators. The overexpression of circRAPGEF5 in LAD tissues and cells indicated that it may be involved in promoting LAD progression. Analysis of 61 LAD tissues revealed that circRAPGEF5 was related to lymph node metastasis. Functionally, circRAPGEF5 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition of LAD cells in vitro and promoted LAD cells growth in vivo. Mechanistically, dual-luciferase reporter assays confirmed direct interaction of circRAPGEF5, miR-1236-3p, and ZEB1. miR-1236-3p was upregulated and ZEB1 expression reduced after circRAPGEF5 knockdown, and the proliferation, migration, and invasion of LAD cells was inhibited. circRAPGEF5 was significantly overexpressed in LAD cell exosomes, and co-culture experiments showed that exosomal circRAPGEF5 enhanced the metastatic ability of LAD cells. Further experiments found that serum exosomal circRAPGEF5 was overexpressed in LAD; moreover, the area under the receiver operator characteristic curve of exosomal circRAPGEF5 was superior to that of serum carcinoembryonic antigen (CEA). Jointly detected serum exosomal circRAPGEF5 and serum CEA had better diagnostic performance than when detected individually. Thus, exosomal circRAPGEF5 could promote the proliferation and metastasis of LAD via the miR-1236-3p/ZEB1 axis and serum exosomal circRAPGEF5 may serve as a promising biomarker for LAD.

Keywords: lung adenocarcinoma, circRAPGEF5, exosomes, proliferation, metastasis