Autophagy-associated circRNA circCDYL augments autophagy and promotes breast cancer progression.

Abstract:

BACKGROUND:Although both circular RNAs (circRNAs) and autophagy are associated with the function of breast cancer (BC), whether circRNAs regulate BC progression via autophagy remains unknown. In this study, we aim to explore the regulatory mechanisms and the clinical significance of autophagy-associated circRNAs in BC. METHODS:Autophagy associated circRNAs were screened by circRNAs deep sequencing and validated by qRT-PCR in BC tissues with high- and low- autophagic level. The biological function of autophagy associated circRNAs were assessed by plate colony formation, cell viability, transwells, flow cytometry and orthotopic animal models. For mechanistic study, RNA immunoprecipitation, circRNAs pull-down, Dual luciferase report assay, Western Blot, Immunofluorescence and Immunohistochemical staining were performed. RESULTS:An autophagy associated circRNA circCDYL was elevated by 3.2 folds in BC tissues as compared with the adjacent non-cancerous tissues, and circCDYL promoted autophagic level in BC cells via the miR-1275-ATG7/ULK1 axis; Moreover, circCDYL enhanced the malignant progression of BC cells in vitro and in vivo. Clinically, increased circCDYL in the tumor tissues and serum of BC patients was associated with higher tumor burden, shorter survival and poorer clinical response to therapy. CONCLUSIONS:circCDYL promotes BC progression via the miR-1275-ATG7/ULK1-autophagic axis and circCDYL could act as a potential prognostic and predictive molecule for breast cancer patients.

journal_name

Mol Cancer

journal_title

Molecular cancer

authors

Liang G,Ling Y,Mehrpour M,Saw PE,Liu Z,Tan W,Tian Z,Zhong W,Lin W,Luo Q,Lin Q,Li Q,Zhou Y,Hamai A,Codogno P,Li J,Song E,Gong C

doi

10.1186/s12943-020-01152-2

subject

Has Abstract

pub_date

2020-03-25 00:00:00

pages

65

issue

1

issn

1476-4598

pii

10.1186/s12943-020-01152-2

journal_volume

19

pub_type

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