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Updated: Dec 7, 2025

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
Published on: June 16, 2018
A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking
Emily B Harrison1,2, Alessandro Porrello1, Brittany M Bowman1
1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
Abstract:
Lung squamous carcinoma (LUSC) is a highly metastatic disease with a poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of circRNA is through miRNA sponging, we found that miR-671-5p more potently silenced an axis of CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing of CDR1as or CDR1 significantly inhibited LUSC metastases and CDR1 was sufficient to promote migration and metastases. CDR1, which directly interacted with adaptor protein 1 (AP1) complex subunits and coatomer protein I (COPI) proteins, no longer promoted migration upon blockade of Golgi trafficking. Therapeutic inhibition of the CDR1as/CDR1 axis with miR-671-5p mimics reduced metastasis in vivo. This report demonstrates a novel role for CDR1 in promoting metastasis and Golgi trafficking. These findings reveal an miRNA/circRNA axis that regulates LUSC metastases through a previously unstudied protein, CDR1. SIGNIFICANCE: This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1.
Insights
MicroRNA-671-5p inhibits lung squamous cell carcinoma (LUSC) metastasis by targeting the CDR1as/CDR1 axis. This axis promotes cancer cell migration and Golgi trafficking, offering a new therapeutic target for LUSC.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Lung squamous cell carcinoma (LUSC) is a metastatic cancer with poor patient outcomes.
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer progression.
- The function of CDR1as and its associated transcript CDR1 in LUSC metastasis is not well understood.
Purpose of the Study:
- To investigate the role of the miR-671-5p/CDR1as/CDR1 axis in LUSC metastasis.
- To identify novel therapeutic targets for reducing LUSC metastasis.
Main Methods:
- Integrated screening approach to identify regulatory interactions.
- Analysis of microRNA (miRNA) and circRNA functions in LUSC cells.
- Investigation of protein interactions and cellular trafficking pathways.
- In vivo studies using therapeutic inhibition of the identified axis.
Main Results:
- miR-671-5p inhibits LUSC metastasis by targeting the CDR1as/CDR1 axis.
- CDR1, the antisense transcript of CDR1as, promotes LUSC cell migration and metastasis.
- CDR1 interacts with AP1 and COPI proteins, influencing Golgi trafficking.
- Therapeutic inhibition of the CDR1as/CDR1 axis with miR-671-5p mimics reduced LUSC metastasis in vivo.
Conclusions:
- The circRNA CDR1as/CDR1 axis plays a significant role in promoting LUSC metastasis and Golgi trafficking.
- miR-671-5p acts as a tumor suppressor by inhibiting this axis.
- The CDR1as/CDR1 axis represents a novel therapeutic target for LUSC.
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