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

Breast Cancer Research

Research

Yuhan Jin¹  Yajie Wang¹  Yaming Li¹  Xi Chen¹  Dianwen Han¹  Fangzhou Ye¹  Liyu Jiang¹  Dan Luo¹  Zekun Wang¹  Yiran Liang¹  Qifeng Yang²  Bing Chen³  Lijuan Wang³  Wenjing Zhao³ 

[1] Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xi Road No. 107, 250012, Jinan, Shandong, China;Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xi Road No. 107, 250012, Jinan, Shandong, China;Pathology Tissue Bank, Qilu Hospital of Shandong University, 250012, Jinan, Shandong, China;Research Institute of Breast Cancer, Shandong University, 250012, Jinan, Shandong, China;Research Institute of Breast Cancer, Shandong University, 250012, Jinan, Shandong, China;

关键词: Triple-negative breast cancer;    MIDEAS-AS1;    MATR3;    NCALD;    Prognosis;   

DOI  :  10.1186/s13058-023-01709-1

 received in 2023-05-30, accepted in 2023-09-11,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTriple-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.MethodsBased 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.ResultsLncRNA 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.ConclusionsCollectively, 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.

【 授权许可】

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

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