Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALD
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-023-01709-1 |
| _version_ | 1827707525776015360 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Dan Luo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T16:48:48Z |
| format | Article |
| id | doaj.art-7327a182b2c044528901ba7944b4436f |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-03-10T16:48:48Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-7327a182b2c044528901ba7944b4436f2023-11-20T11:22:02ZengBMCBreast Cancer Research1465-542X2023-09-0125112010.1186/s13058-023-01709-1Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALDDan Luo0Yiran Liang1Yajie Wang2Fangzhou Ye3Yuhan Jin4Yaming Li5Dianwen Han6Zekun Wang7Bing Chen8Wenjing Zhao9Lijuan Wang10Xi Chen11Liyu Jiang12Qifeng Yang13Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityResearch Institute of Breast Cancer, Shandong UniversityResearch Institute of Breast Cancer, Shandong UniversityResearch Institute of Breast Cancer, Shandong UniversityDepartment of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityAbstract 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.https://doi.org/10.1186/s13058-023-01709-1Triple-negative breast cancerMIDEAS-AS1MATR3NCALDPrognosis |
| spellingShingle | 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 Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALD Breast Cancer Research Triple-negative breast cancer MIDEAS-AS1 MATR3 NCALD Prognosis |
| title | Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALD |
| title_full | Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALD |
| title_fullStr | Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALD |
| title_full_unstemmed | Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALD |
| title_short | Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALD |
| title_sort | long non coding rna mideas as1 inhibits growth and metastasis of triple negative breast cancer via transcriptionally activating ncald |
| topic | Triple-negative breast cancer MIDEAS-AS1 MATR3 NCALD Prognosis |
| url | https://doi.org/10.1186/s13058-023-01709-1 |
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