| Literature DB >> 32978168 |
Emily B Harrison1,2, Alessandro Porrello1, Brittany M Bowman1, Adam R Belanger3, Gabriella Yacovone1, Salma H Azam1, Ian A Windham4, Subrata K Ghosh1, Menglin Wang2, Nicholas Mckenzie1, Trent A Waugh1, Amanda E D Van Swearingen1, Stephanie M Cohen1, Devon G Allen5, Tyler J Goodwin2, Teresa Mascenik5, James E Bear4, Sarah Cohen4, Scott H Randell4,5, Pierre P Massion6, Michael B Major1, Leaf Huang2, Chad V Pecot7,2,8,9.
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. ©2020 American Association for Cancer Research.Entities:
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Year: 2020 PMID： 32978168 PMCID： PMC7669576 DOI： 10.1158/0008-5472.CAN-20-1162
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701