J Cancer 2020; 11(14):4222-4229. doi:10.7150/jca.38830

Research Paper

circNFIC suppresses breast cancer progression by sponging miR-658

Gaosheng Xu1, Dongmei Ye2, Qiang Zhao3, Rongfang He3, Wei Ma1, Yuxuan Li2, Shujie Tang4, Zhiwei Zhou4, Xing Li5,✉, Zhiwei Zhang1,2,✉

1. Yueyang Maternal and Child Health Hospital, Yueyang; Innovative Practice Base for Postgraduate Training of Basic Medicine and Clinical Collaboration, University of South China and Yueyang Maternal and Child Health Hospital, Yueyang 414000, Hunan Province, China.
2. Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Cancer Research Institute of Hengyang Medical College, University of South China, Hengyang, 421001, Hunan Province, China;
3. Department of Pathology, the First Affiliated Hospital of University of South China, Hengyang, 421001, Hunan Province, China;
4. Clinical Medicine Undergraduate Program, Medical College, University of South China, Hengyang, 421001, Hunan Province, China.
5. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China
Gaosheng Xu and Dongmei Ye contributed equally to this work.

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Citation:
Xu G, Ye D, Zhao Q, He R, Ma W, Li Y, Tang S, Zhou Z, Li X, Zhang Z. circNFIC suppresses breast cancer progression by sponging miR-658. J Cancer 2020; 11(14):4222-4229. doi:10.7150/jca.38830. Available from http://www.jcancer.org/v11p4222.htm

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Abstract

Background: Circular RNAs (circRNAs) have been reported to play important roles in cancer progression. However, the potential involvement of circRNAs in breast cancer metastasis to the lung remains unclear.

Methods: High-throughput circular RNA microarray assays of primary breast cancer tissues and lung metastatic tissues were performed. Reactome pathway analysis and GO analysis of the linear mRNA transcripts corresponding to the circRNAs were conducted. The expression of the top downregulated circRNA was confirmed by qRT-PCR in breast cancer cell lines. Kaplan-Meier survival analysis was conducted to analyze the clinical significance of the selected circRNA in breast cancer. A series of in vitro and in vivo experiments, including cell proliferation and migration, was performed to explore the functions of the selected circRNA in breast cancer progression. We further investigated the regulatory effect of the selected circRNA on a miRNA and its target genes to explore the potential mechanisms.

Results: We found that circNFIC (hsa_circ_0002018) was the most downregulated circRNA in lung metastatic tissues. Kaplan-Meier survival analysis revealed that low levels of circNFIC were related to poor outcome of breast cancer. Further experiments revealed that overexpressing circNFIC suppressed breast cancer cell proliferation and migration to the lung. A mechanistic study showed that circNFIC acted as a sponge for miR-658 and competed for binding to miR-658 with UPK1A, leading to increased expression of UPK1A.

Conclusion: Our study highlighted the regulatory function of the circNFIC/miR-658/UPK1A pathway in breast cancer progression, which could be a potential therapeutic target for breast cancer.

Keywords: breast cancer, circRNA, competitive endogenous RNA, proliferation, migration