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

• DOI: 10.1186/s13058-023-01709-1
• Publication Date: 2023-09-28T16:02:34Z
• Authors: Dan Luo; Yiran Liang; Yajie Wang; Fangzhou Ye; Yuhan Jin; Yaming Li; Dianwen Han; Zekun Wang; Bing Chen; Wenjing Zhao; Lijuan Wang; Xi Chen; Liyu Jiang; Qifeng Yang
• Keywords: NCALD; Research; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; RNA-Binding Proteins; Triple Negative Breast Neoplasms; MIDEAS-AS1; Prognosis; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; MATR3; Triple-negative breast cancer; Nuclear Matrix-Associated Proteins; Neurocalcin; Cell Line, Tumor; Humans; RNA, Long Noncoding; RC254-282; Cell Proliferation

Abstract 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.