A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking
Year: 2020
Type: article
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.
Source: Cancer Research
Authors: 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
Language: English
Topic: Circular RNAs in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: American Society of Clinical Oncology, Free To Breathe, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Awards: G1400056210, CAROLINA CANCER NANOTECHNOLOGY TRAINING PROGRAM (C-CNTP), G2262217435, NRSA in Genetics, G407118926, G4126106502, G4441699527, G4568704509, 2/2 NCCU-LCCC Partnership in Cancer Research, G6059871897, Development of EFTX-001 to target KRAS mutations in cancer, Multidisciplinary research training in pulmonary diseases, North Carolina Translational and Clinical Science Institute (NC TraCS), G7149059628, G726513172, G7366156696, Immune Regulation of Lung Squamous Metastasis, G7835072937, Training in Mechanistic, Interdisciplinary Studies of Biological Systems, G866671421, G9000033364, G9000227828, Systematic Analysis of the Actin Cytoskeleton and Directed Cell Migration, Composition and Function of Membrane Contact Sites in Differentiation and Disease, Cancer Center Support Grant, UNC Cystic Fibrosis Research and Translation Core Center
OpenAlex ID: W3088988818