LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis
Abstract Background Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are aberrantly expressed in various cancers. However, the functional roles of lncRNAs in breast cancer remain largely unknown. Methods Based on public databases and integrating bioinformatics analyses, the...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-05-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12943-020-01206-5 |
| _version_ | 1818385118272684032 |
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| author | Yiran Liang Xiaojin Song Yaming Li Bing Chen Wenjing Zhao Lijuan Wang Hanwen Zhang Ying Liu Dianwen Han Ning Zhang Tingting Ma Yajie Wang Fangzhou Ye Dan Luo Xiaoyan Li Qifeng Yang |
| author_facet | Yiran Liang Xiaojin Song Yaming Li Bing Chen Wenjing Zhao Lijuan Wang Hanwen Zhang Ying Liu Dianwen Han Ning Zhang Tingting Ma Yajie Wang Fangzhou Ye Dan Luo Xiaoyan Li Qifeng Yang |
| author_sort | Yiran Liang |
| collection | DOAJ |
| description | Abstract Background Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are aberrantly expressed in various cancers. However, the functional roles of lncRNAs in breast cancer remain largely unknown. Methods Based on public databases and integrating bioinformatics analyses, the overexpression of lncRNA BCRT1 in breast cancer tissues was detected and further validated in a cohort of breast cancer tissues. The effects of lncRNA BCRT1 on proliferation, migration, invasion and macrophage polarization were determined by in vitro and in vivo experiments. Luciferase reporter assay and RNA immunoprecipitation (RIP) were carried out to reveal the interaction between lncRNA BCRT1, miR-1303, and PTBP3. Chromatin immunoprecipitation (ChIP) and RT-PCR were used to evaluate the regulatory effect of hypoxia-inducible factor-1α (HIF-1α) on lncRNA BCRT1. Results LncRNA BCRT1 was significantly upregulated in breast cancer tissues, which was correlated with poor prognosis in breast cancer patients. LncRNA BCRT1 knockdown remarkably suppressed tumor growth and metastasis in vitro and in vivo. Mechanistically, lncRNA BCRT1 could competitively bind with miR-1303 to prevent the degradation of its target gene PTBP3, which acts as a tumor-promoter in breast cancer. LncRNA BCRT1 overexpression could promote M2 polarization of macrophages, mediated by exosomes, which further accelerated breast cancer progression. Furthermore, lncRNA BCRT1 was upregulated in response to hypoxia, which was attributed to the binding of HIF-1α to HREs in the lncRNA BCRT1 promoter. Conclusions Collectively, these results reveal a novel HIF-1α/lncRNA BCRT1/miR-1303/PTBP3 pathway for breast cancer progression and suggest that lncRNA BCRT1 might be a potential biomarker and therapeutic target for breast cancer. |
| first_indexed | 2024-12-14T03:33:04Z |
| format | Article |
| id | doaj.art-3b652cf1021b4118a5977c20f7f91815 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-14T03:33:04Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-3b652cf1021b4118a5977c20f7f918152022-12-21T23:18:41ZengBMCMolecular Cancer1476-45982020-05-0119112010.1186/s12943-020-01206-5LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axisYiran Liang0Xiaojin Song1Yaming Li2Bing Chen3Wenjing Zhao4Lijuan Wang5Hanwen Zhang6Ying Liu7Dianwen Han8Ning Zhang9Tingting Ma10Yajie Wang11Fangzhou Ye12Dan Luo13Xiaoyan Li14Qifeng Yang15Department of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityPathology Tissue Bank, Qilu Hospital of Shandong UniversityPathology Tissue Bank, Qilu Hospital of Shandong UniversityPathology Tissue Bank, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityPathology Tissue Bank, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityDepartment of Breast Surgery, Qilu Hospital of Shandong UniversityAbstract Background Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are aberrantly expressed in various cancers. However, the functional roles of lncRNAs in breast cancer remain largely unknown. Methods Based on public databases and integrating bioinformatics analyses, the overexpression of lncRNA BCRT1 in breast cancer tissues was detected and further validated in a cohort of breast cancer tissues. The effects of lncRNA BCRT1 on proliferation, migration, invasion and macrophage polarization were determined by in vitro and in vivo experiments. Luciferase reporter assay and RNA immunoprecipitation (RIP) were carried out to reveal the interaction between lncRNA BCRT1, miR-1303, and PTBP3. Chromatin immunoprecipitation (ChIP) and RT-PCR were used to evaluate the regulatory effect of hypoxia-inducible factor-1α (HIF-1α) on lncRNA BCRT1. Results LncRNA BCRT1 was significantly upregulated in breast cancer tissues, which was correlated with poor prognosis in breast cancer patients. LncRNA BCRT1 knockdown remarkably suppressed tumor growth and metastasis in vitro and in vivo. Mechanistically, lncRNA BCRT1 could competitively bind with miR-1303 to prevent the degradation of its target gene PTBP3, which acts as a tumor-promoter in breast cancer. LncRNA BCRT1 overexpression could promote M2 polarization of macrophages, mediated by exosomes, which further accelerated breast cancer progression. Furthermore, lncRNA BCRT1 was upregulated in response to hypoxia, which was attributed to the binding of HIF-1α to HREs in the lncRNA BCRT1 promoter. Conclusions Collectively, these results reveal a novel HIF-1α/lncRNA BCRT1/miR-1303/PTBP3 pathway for breast cancer progression and suggest that lncRNA BCRT1 might be a potential biomarker and therapeutic target for breast cancer.http://link.springer.com/article/10.1186/s12943-020-01206-5LncRNA BCRT1miR-1303PTBP3ProgressionBreast cancer |
| spellingShingle | Yiran Liang Xiaojin Song Yaming Li Bing Chen Wenjing Zhao Lijuan Wang Hanwen Zhang Ying Liu Dianwen Han Ning Zhang Tingting Ma Yajie Wang Fangzhou Ye Dan Luo Xiaoyan Li Qifeng Yang LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis Molecular Cancer LncRNA BCRT1 miR-1303 PTBP3 Progression Breast cancer |
| title | LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis |
| title_full | LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis |
| title_fullStr | LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis |
| title_full_unstemmed | LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis |
| title_short | LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis |
| title_sort | lncrna bcrt1 promotes breast cancer progression by targeting mir 1303 ptbp3 axis |
| topic | LncRNA BCRT1 miR-1303 PTBP3 Progression Breast cancer |
| url | http://link.springer.com/article/10.1186/s12943-020-01206-5 |
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