TY - JOUR
T1 - A circle RNA regulatory axis promotes lung squamous metastasis via CDR1-mediated regulation of golgi trafficking
AU - Harrison, Emily B.
AU - Porrello, Alessandro
AU - Bowman, Brittany M.
AU - Belanger, Adam R.
AU - Yacovone, Gabriella
AU - Azam, Salma H.
AU - Windham, Ian A.
AU - Ghosh, Subrata K.
AU - Wang, Menglin
AU - McKenzie, Nicholas
AU - Waugh, Trent A.
AU - Van Swearingen, Amanda E.D.
AU - Cohen, Stephanie M.
AU - Allen, Devon G.
AU - Goodwin, Tyler J.
AU - Mascenik, Teresa
AU - Bear, James E.
AU - Cohen, Sarah
AU - Randell, Scott H.
AU - Massion, Pierre P.
AU - Major, Michael B.
AU - Huang, Leaf
AU - Pecot, Chad V.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/11/15
Y1 - 2020/11/15
N2 - 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-671-5pmore 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. Significance: This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1.
AB - 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-671-5pmore 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. Significance: This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1.
UR - http://www.scopus.com/inward/record.url?scp=85100302084&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-20-1162
DO - 10.1158/0008-5472.CAN-20-1162
M3 - Article
C2 - 32978168
AN - SCOPUS:85100302084
SN - 0008-5472
VL - 80
SP - 4972
EP - 4985
JO - Cancer research
JF - Cancer research
IS - 22
ER -