Autophagy-associated circRNA circCDYL augments autophagy and promotes breast cancer progression.
Adult
Aged
Aged, 80 and over
Animals
Apoptosis
Autophagy
Autophagy-Related Protein 7
/ genetics
Autophagy-Related Protein-1 Homolog
/ genetics
Biomarkers, Tumor
/ genetics
Breast Neoplasms
/ genetics
Cell Proliferation
Co-Repressor Proteins
/ genetics
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Humans
Hydro-Lyases
/ genetics
Intracellular Signaling Peptides and Proteins
/ genetics
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs
/ genetics
Middle Aged
Prognosis
RNA, Circular
/ genetics
Survival Rate
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Autophagy
Breast cancer
circCDYL
miRNA sponge
Journal
Molecular cancer
ISSN: 1476-4598
Titre abrégé: Mol Cancer
Pays: England
ID NLM: 101147698
Informations de publication
Date de publication:
25 03 2020
25 03 2020
Historique:
received:
23
06
2019
accepted:
13
02
2020
entrez:
28
3
2020
pubmed:
28
3
2020
medline:
3
2
2021
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32213200
doi: 10.1186/s12943-020-01152-2
pii: 10.1186/s12943-020-01152-2
pmc: PMC7093993
doi:
Substances chimiques
Biomarkers, Tumor
0
Co-Repressor Proteins
0
Intracellular Signaling Peptides and Proteins
0
MIRN1275 microRNA, human
0
MicroRNAs
0
RNA, Circular
0
Autophagy-Related Protein-1 Homolog
EC 2.7.11.1
ULK1 protein, human
EC 2.7.11.1
CDYL protein, human
EC 4.2.1.-
Hydro-Lyases
EC 4.2.1.-
ATG7 protein, human
EC 6.2.1.45
Autophagy-Related Protein 7
EC 6.2.1.45
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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