circNFIC suppresses breast cancer progression by sponging miR-658
| Autor: | Qiang Zhao, Gaosheng Xu, Zhiwei Zhou, Xing Li, Rongfang He, Shujie Tang, Zhiwei Zhang, Dongmei Ye, Yuxuan Li, Wei Ma |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Messenger RNA Microarray Cell growth business.industry proliferation Cancer migration medicine.disease 03 medical and health sciences breast cancer 030104 developmental biology 0302 clinical medicine Breast cancer Oncology Circular RNA 030220 oncology & carcinogenesis microRNA competitive endogenous RNA medicine Cancer research circRNA business Survival analysis Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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