PXD012286

PXD012286 is an original dataset announced via ProteomeXchange.

Title	A microRNA/circle RNA axis promotes metastasis through CDR1-mediated anoikis-resistance
Description	Lung cancer is an intrinsically highly metastatic disease and the leading cause of cancer-related deaths worldwide. Although discovery of molecular aberrations in lung adenocarcinomas has led to development of effective targeted therapies, corresponding “drivers” in lung squamous carcinomas (LUSC) have not materialized. Extensive molecular profiling has revealed LUSC tumors have non-recurrent somatic mutations and are largely driven by copy number alterations. Because microRNAs (miRs) play increasingly important roles in regulating metastasis-relevant pathways, we evaluated whether miRs can regulate LUSC progression. By integrating bioinformatics of the Cancer Genome Atlas (TCGA) with novel, highly metastatic LUSC models, we found that miR-671-5p is a key inhibitor of LUSC metastasis. Surprisingly, miR-671-5p regulates LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of CDR1as is through miR-7 sponging, we found miR-671-5p more potently silences an axis of CDR1as and its anti-sense transcript, cerebellar degeneration related antigen 1 (CDR1). To our knowledge, no function of CDR1 has ever been described. We found loss of CDR1as and CDR1 significantly inhibited LUSC metastases. Intriguingly, CDR1 was strongly associated with an epithelial-mesenchymal transition (EMT) program in LUSC tumors, and was sufficient to promote metastases, increased migration and substrate-independent survival, known as anoikis-resistance. CDR1, which directly interacts with AP1 and COPI subunits, no longer promoted migration and anoikis-resistance upon blockade of Golgi trafficking. Our findings reveal a miR/circRNA axis that regulates LUSC metastases through an enigmatic protein, CDR1.
HostingRepository	PRIDE
AnnounceDate	2021-09-08
AnnouncementXML	Submission_2021-09-08_08:45:28.328.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brittany Bowman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-09 03:50:01	ID requested
⏵ 1	2021-09-08 08:45:29	announced

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, A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking. Cancer Res, 80(22):4972-4985(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, Lung, Squamous, Cancer, CDR1

Michael B. Major
contact affiliation	Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, United States.
contact email	ben_major@med.unc.edu
lab head
Brittany Bowman
contact affiliation	University of North Carolina at Chapel Hill
contact email	bowbritt@email.unc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD012286

PRIDE project URI

• PRIDE
  1. PXD012286
     1. Label: PRIDE project
     2. Name: A microRNA/circle RNA axis promotes metastasis through CDR1-mediated anoikis-resistance