A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking.

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. ©2020 American Association for Cancer Research.

Citation

Emily B Harrison, Alessandro Porrello, Brittany M Bowman, Adam R Belanger, Gabriella Yacovone, Salma H Azam, Ian A Windham, Subrata K Ghosh, Menglin Wang, Nicholas Mckenzie, Trent A Waugh, Amanda E D Van Swearingen, Stephanie M Cohen, Devon G Allen, Tyler J Goodwin, Teresa Mascenik, James E Bear, Sarah Cohen, Scott H Randell, Pierre P Massion, Michael B Major, Leaf Huang, Chad V Pecot. A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking. Cancer research. 2020 Nov 15;80(22):4972-4985

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PMID: 32978168

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