Circular RNA circFBXO7 attenuates non-small cell lung cancer tumorigenesis by sponging miR-296-3p to facilitate KLF15-mediated transcriptional activation of CDKN1A

Zi-Hao Wang; Lin-Lin Ye; Xuan Xiang; Xiao-Shan Wei; Yi-Ran Niu; Wen-Bei Peng; Si-Yu Zhang; Pei Zhang; Qian-Qian Xue; Hao-Lei Wang; Yi-Heng Du; Yao Liu; Jia-Qi Ai; Qiong Zhou

doi:10.1016/j.tranon.2023.101635

Circular RNA circFBXO7 attenuates non-small cell lung cancer tumorigenesis by sponging miR-296-3p to facilitate KLF15-mediated transcriptional activation of CDKN1A

Transl Oncol. 2023 Apr:30:101635. doi: 10.1016/j.tranon.2023.101635. Epub 2023 Feb 10.

Authors

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Respiratory and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhouqiongtj@hust.edu.cn.

Abstract

Background: Accumulating evidence indicates that circular RNAs (circRNAs) play important roles in various cancers. Hsa_circ_0008832 (circFBXO7) is a circRNA generated from the second exon of the human F-box only protein 7 (FBXO7). Mouse circFbxo7 is a circRNA generated from the second exon of mouse F-box only protein 7 (Fbxo7). The role of human circFBXO7 and mouse circFbxo7 in non-small cell lung cancer (NSCLC) has not been reported.

Methods: The expression of circFBXO7 was measured by quantitative real-time PCR. Survival analysis was performed to explore the association between the expression of circFBXO7 and the prognosis of patients with NSCLC. Lung cancer cell lines were transfected with plasmids. Cell proliferation, cell cycle, and tumorigenesis were evaluated to assess the effects of circFBXO7. Fluorescence in situ hybridization assay was used to identify the location of circFBXO7 and circFbxo7 in human and mouse lung cancer cells. Luciferase reporter assay was conducted to confirm the relationship between circFBXO7 and microRNA.

Results: In this study, we found that circFBXO7 was downregulated in NSCLC tissues and cell lines. NSCLC patients with high circFBXO7 expression had prolonged overall survival. Overexpression of circFBXO7 inhibited cell proliferation both in vitro and in vivo. Mechanistically, we demonstrated that circFBXO7 upregulated the expression of miR-296-3p target gene Krüppel-like factor 15 (KLF15) and KLF15 transactivated the expression of CDKN1A.

Conclusions: CircFBXO7 acts as a tumor suppressor by a novel circFBXO7/miR-296-3p/KLF15/CDKN1A axis, which may serve as a potential biomarker and therapeutic target for NSCLC.

Keywords: CDKN1A; Circular RNAs; KLF15; Non-small cell lung cancer; miR-296-3p.