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Updated: Dec 22, 2025

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
Published on: June 7, 2016
circNFIC suppresses breast cancer progression by sponging miR-658
Gaosheng Xu1, Dongmei Ye2, Qiang Zhao3
1Yueyang 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.
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.
Insights
Circular RNAs (circRNAs) like circNFIC are crucial in breast cancer metastasis. Lower circNFIC levels correlate with poor outcomes, and its restoration inhibits cancer cell spread to the lungs.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in cancer progression.
- The role of circRNAs in breast cancer lung metastasis is not fully understood.
Purpose of the Study:
- To investigate the role of circRNAs in breast cancer metastasis to the lung.
- To identify specific circRNAs involved in this process and elucidate their mechanisms.
Main Methods:
- High-throughput circRNA microarray analysis of primary breast cancer and lung metastatic tissues.
- Bioinformatic analysis (Reactome, GO) of corresponding linear mRNAs.
- qRT-PCR, Kaplan-Meier survival analysis, in vitro/in vivo functional assays, and mechanistic studies (miRNA sponging).
Main Results:
- circNFIC (hsa_circ_0002018) was identified as the most downregulated circRNA in lung metastatic tissues.
- Low circNFIC expression is associated with poor breast cancer prognosis.
- Overexpression of circNFIC inhibited breast cancer cell proliferation and lung metastasis.
- circNFIC functions as a sponge for miR-658, increasing UPK1A expression.
Conclusions:
- The circNFIC/miR-658/UPK1A pathway plays a significant role in breast cancer progression and metastasis.
- circNFIC represents a potential therapeutic target for breast cancer treatment.
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