Dataset Information

A microRNA/circle RNA axis promotes metastasis through CDR1-mediated anoikis-resistance

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Kidney Epithelial Cell, Cell Culture

DISEASE(S): Lung Squamous Cell Carcinoma

SUBMITTER: Brittany Bowman

LAB HEAD: Michael B. Major

PROVIDER: PXD012286 | Pride | 2021-09-08

REPOSITORIES: Pride

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Publications

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

Harrison Emily B EB Porrello Alessandro A Bowman Brittany M BM Belanger Adam R AR Yacovone Gabriella G Azam Salma H SH Windham Ian A IA Ghosh Subrata K SK Wang Menglin M Mckenzie Nicholas N Waugh Trent A TA Van Swearingen Amanda E D AED Cohen Stephanie M SM Allen Devon G DG Goodwin Tyler J TJ Mascenik Teresa T Bear James E JE Cohen Sarah S Randell Scott H SH Massion Pierre P PP Major Michael B MB Huang Leaf L Pecot Chad V CV

Cancer research 20200925 22

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 metast ...[more]

PMID: 32978168

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Dataset Information

A microRNA/circle RNA axis promotes metastasis through CDR1-mediated anoikis-resistance

Publications

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

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