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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Harrison, EB; Porrello, A; Bowman, BM; Belanger, AR; Yacovone, G; Azam, SH; Windham, IA; Ghosh, SK; Wang, M; Mckenzie, N; Waugh, TA; Van Swearingen, AED; Cohen, SM; Allen, DG; Goodwin, TJ; Mascenik, T; Bear, JE; Cohen, S; Randell, SH; Massion, PP; Major, MB; Huang, L; Pecot, CV

Published Date

  • November 2020

Published In

Volume / Issue

  • 80 / 22

Start / End Page

  • 4972 - 4985

PubMed ID

  • 32978168

Pubmed Central ID

  • PMC7669576

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.can-20-1162

Language

  • eng