Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALD

© 2023. BioMed Central Ltd., part of Springer Nature..

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with higher aggressiveness and poorer outcomes. Recently, long non-coding RNAs (lncRNAs) have become the crucial gene regulators in the progression of human cancers. However, the function and underlying mechanisms of lncRNAs in TNBC remains unclear.

METHODS: Based on public databases and bioinformatics analyses, the low expression of lncRNA MIDEAS-AS1 in breast cancer tissues was detected and further validated in a cohort of TNBC tissues. The effects of MIDEAS-AS1 on proliferation, migration, invasion were determined by in vitro and in vivo experiments. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were carried out to reveal the interaction between MIDEAS-AS1 and MATR3. Luciferase reporter assay, Chromatin immunoprecipitation (ChIP) and qRT-PCR were used to evaluate the regulatory effect of MIDEAS-AS1/MATR3 complex on NCALD.

RESULTS: LncRNA MIDEAS-AS1 was significantly downregulated in TNBC, which was correlated with poor overall survival (OS) and progression-free survival (PFS) in TNBC patients. MIDEAS-AS1 overexpression remarkably inhibited tumor growth and metastasis in vitro and in vivo. Mechanistically, MIDEAS-AS1 mainly located in the nucleus and interacted with the nuclear protein MATR3. Meanwhile, NCALD was selected as the downstream target, which was transcriptionally regulated by MIDEAS-AS1/MATR3 complex and further inactivated NF-κB signaling pathway. Furthermore, rescue experiment showed that the suppression of cell malignant phenotype caused by MIDEAS-AS1 overexpression could be reversed by inhibition of NCALD.

CONCLUSIONS: Collectively, our results demonstrate that MIDEAS-AS1 serves as a tumor-suppressor in TNBC through modulating MATR3/NCALD axis, and MIDEAS-AS1 may function as a prognostic biomarker for TNBC.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

Breast cancer research : BCR - 25(2023), 1 vom: 28. Sept., Seite 109

Sprache:

Englisch

Beteiligte Personen:

Luo, Dan [VerfasserIn]
Liang, Yiran [VerfasserIn]
Wang, Yajie [VerfasserIn]
Ye, Fangzhou [VerfasserIn]
Jin, Yuhan [VerfasserIn]
Li, Yaming [VerfasserIn]
Han, Dianwen [VerfasserIn]
Wang, Zekun [VerfasserIn]
Chen, Bing [VerfasserIn]
Zhao, Wenjing [VerfasserIn]
Wang, Lijuan [VerfasserIn]
Chen, Xi [VerfasserIn]
Jiang, Liyu [VerfasserIn]
Yang, Qifeng [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
MATR3
MATR3 protein, human
MIDEAS-AS1
MicroRNAs
NCALD
NCALD protein, human
Neurocalcin
Nuclear Matrix-Associated Proteins
Prognosis
RNA, Long Noncoding
RNA-Binding Proteins
Research Support, Non-U.S. Gov't
Triple-negative breast cancer

Anmerkungen:

Date Completed 02.10.2023

Date Revised 21.11.2023

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s13058-023-01709-1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM362672105